From owner-sci-resources@net.bio.net Sun Aug 01 23:00:00 1993 Path: biosci!NET.BIO.NET!kristoff From: kristoff@NET.BIO.NET (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NSF - Summary of new documents on STIS - 1 August 1993 Message-ID: Date: 2 Aug 93 20:54:54 GMT Sender: kristoff@net.bio.net Distribution: bionet Lines: 82 Approved: sci-resources-moderator@net.bio.net ** NEW DOCUMENTS ON STIS ** Document Type: Dir of Awards Title: NSF 93-59 -- ARCTIC SCIENCE, ENGINEERING, AND EDUCATION File size (bytes): 409276 STIS Filename: nsf9359 Document Type: Program Guideline Title: NSF 93-66 -- Earth Science Research at the National Science Foundation File size (bytes): 48602 STIS Filename: nsf9366 Document Type: Recruit Title: Program Assistant (Office Automation) File size (bytes): 4866 STIS Filename: vgs9381 ------------------------------------------------------------------------ ** UPDATES TO EXISTING STIS DOCUMENTS ** Document Type: Phone Book Title: NSF Alphabetical Listing File size (bytes): 91127 STIS Filename: phnalpha Title: NSF Organizational Directory File size (bytes): 98927 STIS Filename: phnorg Document Type: Recruit Title: Clerical and Administrative Support Positions File size (bytes): 4118 STIS Filename: vgs9373 ------------------------------------------------------------------------ ** FOR YOUR REFERENCE ** ------------------------------------------------------------------------ HOW TO OBTAIN DOCUMENTS The above files can be retrieved in electronic form using the STIS system. If you don't know how to use STIS, send an E-mail message to stisinfo@nsf.gov (Internet) or stisinfo@NSF (BITNET). You will receive a copy of the STIS flyer via E-mail. If you are already using STIS, you can use the information above to retrieve these files: Documents via E-mail: Send a message to stisserv@nsf.gov (Internet) or stisserv@NSF (BITNET). Use the "STIS Filename" shown above in the "get" command. For example, to retrieve vgs9373, the text of your message should be as follows: get vgs9373 Anonymous FTP: FTP to stis.nsf.gov. Use the "STIS Filename" shown above to retrieve a file. For example, to retrieve vgs9373, you would enter: ftp> get vgs9373 WAIS or Gopher: Do a word search on the filename as shown in the summary. If you want a *printed* copy of a document: Send your name and postal mailing address, and the document title and number to "firstop@nsf.gov" (Internet) or "firstop@nsf" (BITNET). If you have problems with the above procedures: Send a message to "stis@nsf.gov" (Internet) or "stis@NSF" (BITNET). From owner-sci-resources@net.bio.net Thu Aug 05 23:00:00 1993 Path: biosci!net.bio.net From: kristoff@net.bio.net (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 22, no. 28, pt. 1, 6 August 1993 Message-ID: Date: 6 Aug 93 03:24:05 GMT Sender: kristoff@net.bio.net Lines: 1187 Approved: biosci-moderator@net.bio.net NOTE: The NIH Guide may be split into more than one mail message to avoid truncation during e-mail distribution. The first message always begins with the RFP/RFA summary sections followed by the appended texts of the full RFP/RFAs. ---------------------------------------------------------------------- $$XID NIHGUIDE 19930806 V22N28 P1O1 ************************************ X-comment: RFAs described: HD-94-006, CA-93-037, AI-93-017, AI-93-012 NIH GUIDE - Vol. 22, No. 28 - August 6, 1993 $$INDEX BEGIN ******************************************************* NOTICES OF AVAILABILITY (RFPs AND RFAs) $$INDEX R1 11/19/93 ************************************************* HUMAN FETAL TISSUE CHARACTERIZATION FOR TRANSPLANTATION (RFA HD-94-006) National Institute of Child Health and Human Development National Institute of Diabetes and Digestive and Kidney Diseases National Institute of Neurological Disorders and Stroke INDEX: CHILD HEALTH, HUMAN DEVELOPMENT; DIABETES, DIGESTIVE, KIDNEY DISEASES; NEUROLOGICAL DISORDERS, STROKE $$INDEX R2 11/23/93 ************************************************* ROLE OF THE MICROENVIRONMENT IN BREAST AND PROSTATE CANCER (RFA CA-93-037) National Cancer Institute INDEX: CANCER $$INDEX R3 11/24/93 ************************************************* MULTICOMPONENT VACCINE DEVELOPMENT (RFA AI-93-017) National Institute of Allergy and Infectious Diseases INDEX: ALLERGY, INFECTIOUS DISEASES $$INDEX R4 12/08/93 ************************************************* IMMUNE RECONSTITUTION OF HIV-INFECTED INDIVIDUALS (RFA AI-93-012) National Institute of Allergy and Infectious Diseases National Institute of Diabetes and Digestive and Kidney Diseases INDEX: ALLERGY, INFECTIOUS DISEASES; DIABETES, DIGESTIVE, KIDNEY DISEASES ERRATUM $$INDEX E1 09/17/93 ************************************************* CENTERS FOR AIDS RESEARCH/CORE SUPPORT GRANT (CFAR/CSG) (RFA AI-93- 014) National Institute of Allergy and Infectious Diseases National Institute of Mental Health INDEX: ALLERGY, INFECTIOUS DISEASES; MENTAL HEALTH This publication is available electronically to institutions via BITNET or INTERNET and is also on the NIH GOPHER. Alternative access is through the NIH Grant Line using a personal computer (data line 301/402-2221). Contact Dr. John James at 301/594-7270 for details. $$INDEX END ********************************************************* NOTICES OF AVAILABILITY (RFPs AND RFAs) $$R1 BEGIN HD-94-006 FULL-TEXT ************************************** HUMAN FETAL TISSUE CHARACTERIZATION FOR TRANSPLANTATION NIH GUIDE, Volume 22, Number 28, August 6, 1993 RFA AVAILABLE: HD-94-006 P.T. 34; K.W. 0705035, 0745065, 0780005 National Institute of Child Health and Human Development National Institute of Diabetes and Digestive and Kidney Diseases National Institute of Neurological Disorders and Stroke Letter of Intent Receipt Date: October 1, 1993 Application Receipt Date: November 19, 1993 THIS IS A NOTICE OF AVAILABILITY OF A REQUEST FOR APPLICATIONS (RFA); IT IS ONLY AN ABSTRACT OF THE RFA. POTENTIAL APPLICANTS MUST REQUEST THE COMPLETE RFA, WHICH CONTAINS ESSENTIAL INFORMATION FOR THE PREPARATION OF AN APPLICATION, FROM THE CONTACT LISTED IN "INQUIRIES," BELOW. FAILURE TO FOLLOW THE INSTRUCTIONS IN THE COMPLETE RFA MAY RESULT IN AN INCOMPLETE APPLICATION, WHICH WILL BE RETURNED TO THE APPLICANT WITHOUT REVIEW. PURPOSE This RFA has been developed to encourage research on the standards and methods for identifying and characterizing optimal human fetal tissue for use in transplantation therapy. Joint funding by the National Institute of Child Health and Human Development (NICHD), the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and the National Institute of Neurological Disorders and Stroke (NINDS) reflects the extent of interest in evaluating human fetal tissues and their biological potentials. Attention should be given to proper collection, processing, culturing and preserving these tissues to assure highest quality control. This research should consider addressing methods for acquisition, establishing morphologic status, determining developmental age and viability, assessing sterility and genetic normality, preserving by cryopreservation, and establishing cell lines. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This RFA, Human Fetal Tissue Characterization for Transplantation, is related to the priority areas of maternal and infant health, and diabetes and chronic disabling conditions. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1), through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories and units of state and local governments. Applications from investigators who are minority individuals and women are encouraged. MECHANISM OF SUPPORT This RFA solicits applications that will be awarded as NIH research project grants (R01s). The duration of these awards is to be four years. This announcement is for a single competition and the application receipt date is November 19, 1993. FUNDS AVAILABLE It is anticipated that up to six grants will be awarded under this program, contingent upon receipt of a sufficient number of meritorious applications and the availability of funds. To fund these awards, $1,000,000 has been set aside for the direct costs in the first year. RESEARCH OBJECTIVES The use of human fetal tissue transplants has been advocated for several years as a means of treating a number of devastating diseases. Fetal tissue transplants may allow replacement of tissues and cell products that have been damaged, destroyed, or that never developed properly due to disease or a genetic disorder. These maladies are life threatening unless intervention is instituted. Childhood diseases such as inborn errors of metabolism, immune deficiencies and other entities are being considered for very early treatment using fetus-to-fetus transplants. Diseases such as insulin-dependent diabetes mellitus (IDDM) and Parkinson's Disease are also prospective candidates for transplantation therapy. The results of the Diabetes Control and Complications Trial demonstrate the profound importance of glucose control in the prevention of Diabetic complications. Thus, transplantation therapy offers new avenue for tighter glucose control in IDDM patients. Initial results of surgical transplantation in Parkinson's Disease for a small number of cases hold considerable promise although more definitive study and evaluation are required. There is currently considerable interest in the therapeutic use of fetal tissues for the treatment of incurable and chronic diseases, both from the medical and the basic science community. Methods should be considered to optimize and standardize the handling and processing of fetal tissues as well as their preservation and storage. It is evident that better characterization of these more immature fetal tissues is required to assure optimal therapeutic results. Improved knowledge of the potential of these cells will define their roles in normal developmental processes based on their developmental age and biological potential, and will improve their usefulness in replacement therapy. Tissue Collection Appropriate collaboration with clinicians will be required to obtain necessary tissue in a timely fashion and collected in a manner suitable for the scheduled tissue processing. Accurate assessment of developmental age, gross examination of tissues, and grading of tissues for viability will also require a pathology/teratology assessment. In obtaining medical histories and serological screening of contributors of the products of conception for this research, appropriate informed consent must be obtained. Evaluation of pathogenic contaminants, cytogenetic studies and assessment of genetic mutations in at-risk specimens are research areas to be included. Applicants should be able to demonstrate immunologic and transplantation expertise and have available established tissue culture facilities with the expertise for growing, characterizing, cryopreserving and maintaining suitable fetal cell lines. Data Collection The data from these studies should be used to address the quality and efficacy of the tissues under investigation for transplantation therapy. This information should be applicable to the establishment of protocols and tissue processing innovations. SPECIAL REQUIREMENTS The fetal tissue acquisition and handling must comply with the regulations for Federal Funding of Fetal Tissue Transplantation Research as set forth in the NIH Guide for Grants and Contracts, Volume 22, Number 11, March 19, 1993. It is expected that at least two meetings per year in the Washington, DC area of the awardees, NIH staff, and NIH consultants, during both the first and subsequent years, will be required to assess progress and workscope. These meetings will be of benefit to the grantees and will allow them to address unforeseen difficulties, establish collaborative efforts and assess the schedule of progress. The grantees will retain primary authority and responsibility for the work. Funds for this travel should be requested in the application. STUDY POPULATIONS SPECIAL INSTRUCTIONS FOR INCLUSION OF MINORITIES IN CLINICAL RESEARCH STUDIES For projects involving clinical research, NIH requires applicants to give special attention to the inclusion of women and minorities in study populations. If women or minorities are not included in the study populations for clinical studies, a specific justification for this exclusion must be provided. Applications without such documentation will not be accepted for review. LETTER OF INTENT Prospective applicants are asked to submit, by October 1, 1993, a letter of intent that includes a descriptive title of the proposed research; the name, address, and telephone number of the Principal Investigator; the identities of other key personnel and participating institutions; and the number and title of the RFA in response to which the application may be submitted. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, the information that it contains is helpful in planning for the review of applications. It allows NICHD, NIDDK, and NINDS staff to estimate the potential review workload and to avoid conflict of interest in the review. The letter of intent is to be sent to Dr. Delbert H. Dayton at the address listed under INQUIRIES. APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 9/91) is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research and from the Office of Grants Information, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone (301) 594-7248. The RFA label available in the PHS 398 application form must be affixed to the bottom of the face page. Failure to use this label could result in delayed processing of an application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2a of the face page of the application form and the YES box checked. Submit a signed, typewritten original of the application, including the Checklist, and three signed, exact photocopies, in one package to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** At the time of submission, two additional copies of the application must also be sent to: Susan Streufert, Ph.D. Division of Scientific Review National Institute of Child Health and Human Development 6100 Executive Boulevard, Room 5E03 Bethesda, MD 20892 REVIEW CONSIDERATIONS Applications will be received by the NIH Division of Research Grants and reviewed for completeness. Incomplete applications will be returned to the applicant. NICHD, NIDDK, and NINDS staff will review the applications for responsiveness to the RFA. Applications judged to be nonresponsive will be returned. Responsive applications may be subjected to a triage by a peer-review group to determine the scientific merit relative to the other applications received in response to this RFA. NIH will withdraw from competition those applications judged to be noncompetitive and will notify the applicant and institutional official. Those applications judged to be competitive will be further evaluated for scientific/technical merit by a review group convened solely for this purpose by the Division of Scientific Review, NICHD. Following review by the Initial Review Group, applications will be evaluated by the appropriate assigned Advisory Councils for program relevance and policy issues before awards for meritorious applications are made. INQUIRIES Written and telephone inquiries concerning this RFA are welcome. Direct inquiries regarding programmatic issues, requests for the RFA, and address the letter of intent to: Delbert H. Dayton, M.D. Center for Research for Mothers and Children National Institute of Child Health and Human Development 6100 Executive Boulevard, Room 4B01 Bethesda, MD 20892 Telephone: (301) 496-5541 Joan T. Harmon, Ph.D. Division of Diabetes, Endocrinology and Metabolic Diseases National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 622 Bethesda, MD 20892 Telephone: (301) 594-7565 Eugene J. Oliver, Ph.D. Division of Demyelinating, Atrophic, and Dementing Disorders National Institute of Neurological Disorders and Stroke 7550 Wisconsin Avenue, Room 806 Bethesda, MD 20892 Telephone: (301) 496-1431 Direct inquiries regarding fiscal matters to: Ms. Mary Ellen Colvin Office of Grants and Contracts National Institute of Child Health and Human Development 6100 Executive Boulevard, Room 8A17 Bethesda, MD 20892 Telephone: (301) 496-1303 Ms. Betty E. Bailey Division of Extramural Activities National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 649 Bethesda, MD 20892 Telephone: (301) 594-7543 Mr. George Tucker Division of Extramural Activities National Institute of Neurological Disorders and Stroke 7550 Wisconsin Avenue, Room 1004 Bethesda, MD 20892 Telephone: (301) 496-9231 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance Nos. 93.847, 93.853, 93.854, and 93.865. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. $$R1 END ************************************************************ $$R2 BEGIN CA-93-037 FULL-TEXT ************************************** ROLE OF THE MICROENVIRONMENT IN BREAST AND PROSTATE CANCER NIH GUIDE, Volume 22, Number 28, August 6, 1993 RFA AVAILABLE: CA-93-037 P.T. 34; K.W. 0715036, 1002004, 1002008, 0760025 National Cancer Institute Letter of Intent Receipt Date: September 10, 1993 Application Receipt Date: November 23, 1993 THIS IS A NOTICE OF AVAILABILITY OF A REQUEST FOR APPLICATIONS (RFA); IT IS ONLY AN ABSTRACT OF THE RFA. POTENTIAL APPLICANTS MUST REQUEST THE COMPLETE RFA, WHICH CONTAINS ESSENTIAL INFORMATION FOR THE PREPARATION OF AN APPLICATION, FROM THE CONTACT LISTED IN "INQUIRIES," BELOW. FAILURE TO FOLLOW THE INSTRUCTIONS IN THE COMPLETE RFA MAY RESULT IN AN INCOMPLETE APPLICATION, WHICH WILL BE RETURNED TO THE APPLICANT WITHOUT REVIEW. PURPOSE The Cancer Biology Branch, Division of Cancer Biology, Diagnosis and Centers (DCBDC) at the National Cancer institute (NCI), in collaboration with the Chemical and Physical Carcinogenesis Branch, Division of Cancer Etiology (DCE), NCI, invites investigator-initiated research grant applications to elucidate the molecular interactions among the cell populations of human breast and prostatic cancer that contribute to malignant progression. New and experienced investigators in relevant fields and disciplines may apply for funds to pursue this research. The aim of this RFA is to foster application of recent advances in molecular and cellular biology, using appropriate model systems, to study the effects of tumor cell-stroma interactions relevant to tumor development and progression in human breast and prostatic tissues. A multidisciplinary approach involving interactions among basic and clinical scientists is encouraged. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This RFA, Role of the Microenvironment in Breast and Prostate Cancer, is related to the priority area of cancer. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Research grant applications may be submitted by domestic and foreign for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT Support of this RFA will be by National Institutes of Health (NIH) individual research project grants (R01). Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. The total project period for applications submitted in response to the present RFA may not exceed four years. Awards will be administered under PHS grants policy as stated in Public Health Service Grants Policy Statement, DHHS Publication No. (OASH) 90-50,000, revised October 1, 1990. The anticipated award date is July 1, 1994. This RFA is a one-time solicitation. Future unsolicited competing continuation applications will compete with all investigator-initiated applications and be reviewed according to the customary NIH peer review procedures. FUNDS AVAILABLE Approximately $2,000,000 in total costs per year for up to four years will be committed to fund applications submitted in response to this RFA. It is anticipated that up to twelve awards will be made. This level of support is dependent on the receipt of a sufficient number of applications of high scientific merit. Although this program is provided for in the financial plans of the NCI, awards pursuant to this RFA are contingent upon the availability of funds for this purpose. RESEARCH OBJECTIVES This RFA is intended to encourage a variety of investigator-initiated research projects to use appropriate model systems that take into consideration the highly interactive environment of the tumor cells, as well as the contributions of the tumor and host cells to the growth and metastatic spread of breast or prostatic carcinomas. It is also important to delineate the genetic and environmental factors involved in stromal-epithelial interactions which are relevant to malignant progression of hormonally regulated tumors. It may include collaborations among basic and clinical scientists and should embrace an array of molecular and cellular approaches. Evidence of the establishment of reliable tumor cell systems or relevant tumor models should be included in the application. Applications that propose to explore interactions of the stroma with only normal epithelium will not be considered responsive to the RFA. STUDY POPULATIONS SPECIAL INSTRUCTIONS FOR INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDIES For projects involving clinical research, NIH requires applicants to give special attention to the inclusion of minorities in study populations. If minorities are not included in the study populations for clinical studies, a specific justification for this inclusion must be provided. Applications without such documentation will not be accepted for review. LETTER OF INTENT Prospective applicants are asked to submit, by September 10, 1993, a letter of intent that includes a descriptive title of the proposed research, the name, address, and telephone number of the Principal Investigator, the identities of other key personnel and participating institutions, and the number and title of the RFA in response to which the application may be submitted. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, the information that it contains is helpful in planning for the review of applications. It allows NCI staff to estimate the potential review workload and to avoid conflict of interest in the review. The letter of intent is to be sent to Dr. Suresh Mohla at the address listed under INQUIRIES. APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 9/91) is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research and from the Office of Grants Information, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892-9912, telephone 301/594-7248. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed by the Division of Research Grants (DRG) staff for completeness. Incomplete applications will be returned to the applicant without further consideration. Complete applications will be evaluated by NCI program staff to determine if they are responsive to the program requirements and criteria stated in this RFA. Applications may receive a preliminary scientific peer review (triage) by an NCI peer review group on the basis of relative competitiveness. The NIH will withdraw from further competition those applications judged to be non- competitive for award and notify the applicant Principal Investigator and institutional official. Those applications judged to be responsive and competitive will be further evaluated according to the review criteria stated below for scientific and technical merit by an appropriate peer review group convened by the Division of Extramural Activities, NCI. The second level of review by the National Cancer Advisory Board considers the special needs of the Institute and the priorities of the National Cancer Program. Review criteria for evaluating the scientific merit of this RFA include: o extent to which the proposed research addresses the goals of the RFA o scientific and technical significance and originality of proposed research o appropriateness and adequacy of the experimental approach, and potential relevance of the model system to human breast or prostate cancer o qualifications and research experience of the Principal Investigator and staff o appropriateness of the proposed budget and duration in relation to the proposed research INQUIRIES Written and telephone requests for the RFA and the opportunity to clarify any issues or questions from the potential applicants are welcome. Direct requests for the RFA, inquiries regarding programmatic issues, and address the letter of intent to: Dr. Suresh Mohla Division of Cancer Biology, Diagnosis, and Centers National Cancer Institute Executive Plaza North, Room 505 Bethesda, MD 20892 Telephone: (301) 496-7028 Direct inquiries regarding fiscal matters to: Mr. Robert Hawkins Grants Management Branch National Cancer Institute Executive Plaza South, Room 243 Bethesda, MD 20892 Telephone: (301) 496-7800 ext. 13 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.396, Cancer Biology. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health $$R2 END ************************************************************ $$R3 BEGIN AI-93-017 FULL-TEXT ************************************** MULTICOMPONENT VACCINE DEVELOPMENT NIH GUIDE, Volume 22, Number 28, August 6, 1993 RFA AVAILABLE: AI-93-017 P.T. 34; K.W. 0740075, 1002045, 0710070 National Institute of Allergy and Infectious Diseases Letter of Intent Receipt Date: October 1, 1993 Application Receipt Date: November 24, 1993 THIS IS A NOTICE OF AVAILABILITY OF A REQUEST FOR APPLICATIONS (RFA); IT IS ONLY AN ABSTRACT OF THE RFA. POTENTIAL APPLICANTS MUST REQUEST THE COMPLETE RFA, WHICH CONTAINS ESSENTIAL INFORMATION FOR THE PREPARATION OF AN APPLICATION, FROM THE CONTACT LISTED IN "INQUIRIES," BELOW. FAILURE TO FOLLOW THE INSTRUCTIONS IN THE COMPLETE RFA MAY RESULT IN AN INCOMPLETE APPLICATION, WHICH WILL BE RETURNED TO THE APPLICANT WITHOUT REVIEW. PURPOSE The Division of Microbiology and Infectious Diseases of the National Institute of Allergy and Infectious Diseases (NIAID) announces the availability of an RFA for research that will lead to the design of new innovative approaches for the synthesis and development of combination vaccines. The objective of this project is to examine basic research approaches toward the development of multivalent vaccines which would provide safe and long lasting immunity to multiple agents while providing maximum safety, immunogenicity, and efficacy in the fewest doses possible. Multicomponent (multivalent) combination vaccines containing antigens to viral and/or bacterial components provide many distinct advantages over conventional vaccines and allow for the introduction of "disease-specific", "age-specific" and "duration-specific" designer vaccines. The development of combination vaccines will greatly facilitate the implementation of the universal vaccination programs required to bring under control serious infectious diseases worldwide. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This RFA, Multicomponent Vaccine Development, is related to the priority area of immunization and infectious diseases. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT Awards made under this RFA will use the National Institutes of Health (NIH) individual research project grant (R01). Responsibility for the planning, direction and execution of the proposed project will be solely that of the applicant. The total project period for applications submitted by domestic institutions in response to the present RFA may not exceed four years; the total project period for applications submitted by foreign institutions may not exceed three years. The earliest possible award date is July 1, 1994. Applicants are encouraged to coordinate, through the use of consortium arrangements or subcontracts, integrated approaches with individuals or institutions having relevant reagents and expertise in their use, demonstrated ability in a particular area of relevant research, or access to relevant patient populations so as to accelerate technical progress and clinical development of promising therapies. Because the nature and scope of the research proposed in response to this RFA may vary, it is anticipated that the amounts of the awards will vary also. This RFA is a one-time solicitation. Future competing continuation applications will compete with all unsolicited investigator-initiated applications and be reviewed by an appropriate study section according to customary NIH referral and peer review procedures. FUNDS AVAILABLE The estimated level of support (total direct and indirect costs) for the entire program for the first year is $ 1.5 million. The NIAID anticipates making a minimum of four new awards. RESEARCH OBJECTIVES The ability to selectively eradicate various childhood diseases through the development of immunization programs that incorporate new emerging technologies for the creation of improved, safe and efficacious vaccines is a primary aim of NIAID and also the Children's Vaccine Initiative (CVI) Program. A major concept advanced by this program is the idea of providing fewer doses of vaccine to help facilitate delivery and broaden the coverage of immunization. Barriers to the development of multicomponent vaccines are not merely technological, but will require scientific advances in a number of areas in basic science and infectious diseases. One of the most complex, but basic issues that needs to be resolved is the problem of incorporating fundamentally different products or antigens into a single matrix. For example, at this time we are not able to mix attenuated live agents with killed agents such as oral polio vaccine and Haemophilus influenzae type b conjugate vaccines. The current proposed approach for making combination vaccines is restricted to mixing either a series of antigens or other "like" immunogens in a single dose. Additional research is needed to better understand the immunologic basis for incompatibility/compatibility among disparate antigens. Furthermore, the development of vaccines to diseases that produce systemic infection may differ significantly from those in which infection occurs at mucosal or other epithelial surfaces. One of the many new vaccine strategies focuses on the identification of protective epitopes against specific organisms. Often these organisms represent only one of the many pathogens associated with the disease state. One such example is the complex etiology of pneumonia. A significant aspect of this new vaccine strategy would be to develop vaccines composed of relevant portions of multiple pathogens associated with a particular disease (e.g., pneumonia), or a particular need (e.g., children). The development of large vector systems with ability to express multiple foreign genes using a single injection, or newly constructed novel attenuated viruses with defined genetic mutations may provide opportunities to evaluate this strategic approach. Other strategies include the use of viral peptides, which contain several viral specific epitopes, that could be used as carriers for capsular polysaccharide bacterial antigens from various infectious organisms. The overall major objective of this initiative is to encourage basic research in developing new approaches for making combination vaccines that demonstrate the capacity to protect against multiple human pathogens in the fewest doses possible. Efforts are needed to refocus vaccine development strategies toward attaining maximal clinical outcomes for various childhood diseases using new and creative technologies. These advanced technologies will provide, hopefully, new alternatives to current approaches in viral and bacterial vaccine development. Applicants are encouraged to propose innovative approaches to the production of multicomponent vaccines and to consider other relevant issues such as antigenic competition, stability, valence limitations, antigen processing, and immune recognition and lymphocyte activation. SPECIAL REQUIREMENTS NIAID program staff will organize annual meetings in Bethesda that Principal Investigators and other key members (as designated by the Principal Investigators) of the projects are encouraged to attend to discuss progress. Funds for travel to these meetings should be included in the budget. STUDY POPULATIONS SPECIAL INSTRUCTIONS FOR INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDIES For projects involving clinical research, NIH requires applicants to give special attention to the inclusion of women and minorities in study populations. If women or minorities are not included in the study populations for clinical studies, a specific justification for this exclusion must be provided. Applications without such documentation will not be accepted for review. LETTER OF INTENT Prospective applicants are asked to submit, by October 1, 1993, a letter of intent that includes a descriptive title of the proposed research, the names and affiliations of proposed key investigators, and the number and title of the RFA in response to which the application may be submitted. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, the information that it contains allows NIAID staff to estimate the potential review workload and to avoid possible conflict of interest in the review. The letter of intent is to be sent to Dr. Olivia Preble at the address listed under INQUIRIES. APPLICATION PROCEDURES Applications are to be submitted on form PHS 398 (rev. 9/91), the standard application form for research grants. Application kits are available at most institutional offices of sponsored research and may be obtained from the Office of Grants Information, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone 301/594-7248. Applicants must adhere to the format and requirements specified in the PHS 398 application kit. The receipt date for applications is November 24, 1993. The signed, typewritten original of the application, including the Checklist, and three exact copies must be sent to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** At the time of submission, two additional copies must also be sent to Dr. Olivia Preble at the address listed under INQUIRIES. To ensure their review, applications must be received by both the Division of Research Grants (DRG) and Dr. Olivia Preble by the application receipt date. Applications not received on the receipt date will be considered non-responsive and will be returned to the applicant without review. If the application submitted in response to this RFA is substantially similar to a grant application already submitted to the NIH for review, but which has not yet been reviewed, the applicant will be asked to withdraw either the pending application or the new one. Simultaneous submission of essentially identical applications will not be allowed, nor will essentially identical applications be reviewed by different review committees. Therefore, an application cannot be submitted in response to this RFA that is essentially identical to one that has already been reviewed. This does not preclude the submission of substantial revisions of applications already reviewed, but such applications must include an introduction addressing the previous critique. REVIEW CONSIDERATIONS Applications will be reviewed by DRG staff for completeness and by NIAID staff to determine administrative and programmatic responsiveness to this RFA. Those judged to be incomplete or nonresponsive will be returned to the applicant without review. Those considered complete and responsive may be subjected to a triage review by an NIAID peer review group, before or during the initial review meeting, to determine their scientific merit relative to the other applications submitted in response to this RFA. The NIAID will withdraw from competition those applications judged by the triage peer review group to be noncompetitive for award and will so notify the applicant investigator and the institutional business official. Those applications judged to be competitive for award will be reviewed for scientific and technical merit by a Review Committee convened by the Division of Extramural Activities, NIAID. The second level of review will be provided by the National Advisory Allergy and Infectious Diseases Council. INQUIRIES Written and telephone inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues and requests for the RFA to: Dr. David L. Klein Division of Microbiology and Infectious Diseases National Institute of Allergy and Infectious Diseases Solar Building, Room 3A-10 Bethesda, MD 20892 Telephone: (301) 496-5305 FAX: (301) 402-8030 Send the letter of intent and direct any questions regarding review procedures, to: Dr. Olivia Preble Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Building, Room 4C-19 Bethesda, MD 20892 Telephone: (301) 496-8208 FAX: (301) 402-2638 Direct inquiries regarding fiscal matters to: Mr. Todd Ball Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Building, Room 4B-35 Bethesda, MD 20892 Telephone: (301) 496-7075 FAX: (301) 480-3780 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.856, Microbiology and Infectious Disease Research. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. $$R3 END ************************************************************ $$R4 BEGIN AI-93-012 FULL-TEXT ************************************** IMMUNE RECONSTITUTION OF HIV-INFECTED INDIVIDUALS NIH GUIDE, Volume 22, Number 28, August 6, 1993 RFA AVAILABLE: AI-93-012 P.T. 34; K.W. 0715008, 0710070, 0705040, 0740012, 0745032 National Institute of Allergy and Infectious Diseases National Institute of Diabetes and Digestive and Kidney Diseases Letter of Intent Receipt Date: October 27, 1993 Application Receipt Date: December 8, 1993 THIS IS A NOTICE OF AVAILABILITY OF A REQUEST FOR APPLICATIONS (RFA); IT IS ONLY AN ABSTRACT OF THE RFA. POTENTIAL APPLICANTS MUST REQUEST THE COMPLETE RFA, WHICH CONTAINS ESSENTIAL INFORMATION FOR THE PREPARATION OF AN APPLICATION, FROM THE CONTACT LISTED IN "INQUIRIES," BELOW. FAILURE TO FOLLOW THE INSTRUCTIONS IN THE COMPLETE RFA MAY RESULT IN AN INCOMPLETE APPLICATION, WHICH WILL BE RETURNED TO THE APPLICANT WITHOUT REVIEW. PURPOSE The National Institute of Allergy and Infectious Diseases (NIAID) and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) wish to promote research on interactions of the Human Immunodeficiency Virus-1 (HIV-1) with the immune system that may impact on the immunologic reconstitution of infected individuals; cytokines to facilitate stem cell reconstitution of HIV-infected individuals or ameliorate/reverse HIV-related damage to the immune system; and gene-based strategies to counteract detrimental effects of HIV-1 on the immune system, to prevent infection of stem cells transplanted into HIV-infected individuals, and to improve the characteristics of ex vivo expanded lymphocytes to enable them to function more effectively in vivo. Although clinical trials will not be supported under this RFA, the basic and preclinical research accomplished is expected to lay the foundation for future clinical trials. The NIAID and NIDDK request the coordinated submission of related individual research project grant applications from investigators who wish to collaborate on research, but do not require extensive shared physical resources. These applications must share a common theme and describe the objectives and scientific importance of the interchange of ideas, data, and materials among the collaborating investigators. This collaborative research will be supported by investigator- initiated Interactive Research Project Grant (IRPG). For further information, potential applicants should refer to Special Instructions for Preparing Applications for Interactive Research Project Grants, which may be obtained from the program staff listed under INQUIRIES. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This RFA, Immune Reconstitution of HIV-Infected Individuals, is related to the priority area of HIV infection. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign, for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT The support mechanism for this program will be individual research project grants (R01s) which are organized around a common theme into an IRPG. It is the responsibility of the applicants to plan, direct and execute the proposed projects in accord with their interests and perceptions of potential treatment strategies utilizing immune reconstitution. The total project period for applications submitted in response to the present RFA may not exceed four years. IRPG applications considered responsive to this RFA will have at least two components, one proposing research on stem cell or somatic cell therapies and one proposing gene-based therapeutic strategies. Reissuance of this initiative in future years is anticipated but not certain. FUNDS AVAILABLE The NIAID and NIDDK anticipate awarding two to four IRPGs (a total of six to eight R01 awards), for a total cost of $1.9 million for the initial year of funding. The NIAID has set aside $1.2 million for applications received in response to this RFA, and the NIDDK has set aside $0.7 million for this purpose. RESEARCH OBJECTIVES The long term goal of this RFA is to provide an experimental basis for using immune reconstitution as a therapy in individuals whose immune systems are compromised by infectious disease. This RFA focuses on HIV/AIDS. Research responsive to this RFA includes, but is not limited to, the following: o Research to clarify interactions of HIV with the immune system that may bear on the successful reconstitution of infected individuals and gene-based strategies to counter HIV-related damage to the immune system; o Research on antiviral strategies, including the design and evaluation of new gene-based antiviral strategies to be used in stem cells or other sources of immune cells; o Research to discover and/or develop novel sources of multipotent stem cells that can be genetically engineered to resist HIV-1 infection, new cytokines capable of interacting with T cell progenitor cells or their immediate antecedents, new assays to quantitate T cell progenitor cells. STUDY POPULATIONS SPECIAL INSTRUCTIONS CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS For projects involving clinical research, NIH requires applicants to give special attention to the inclusion of minorities and women in study populations. If women and minorities are not included in the study populations for clinical studies, a specific justification for this exclusion must be provided. Applications without such documentation will not be accepted for review. LETTER OF INTENT Prospective applicants are asked to submit, by October 27, 1993, a letter of intent that includes descriptive titles of each proposed research project in the IRPG group, the names and address of the Principal Investigators and other key personnel, the participating institutions, and the number and title of this RFA. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, the information that it contains allows the NIAID and NIDDK to estimate the potential workload for reviewers and to avoid possible conflict of interest in the review process. The letter of intent is to be sent to Dr. Dianne Tingley at the address indicated in INQUIRIES below. APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 9/91) is to be used in applying for these grants. This form is available at most institutional offices of sponsored research and from the Office of Grants Information, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone (301) 594-7248. Additional instructions for the preparation of interactive project applications will be provided with the RFA. Applications not received by December 8, 1993, will be considered unresponsive and returned to the applicant without review. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed by Division of Research Grants (DRG) for completeness and by NIAID and NIDDK staff to determine responsiveness. Incomplete and non-responsive applications will be returned to the applicant without further consideration or review. Those applications considered responsive to the RFA may be subjected to a triage by a peer review group, before or during the review committee meeting, to determine their scientific merit relative to the other applications submitted in response to this RFA. The NIAID will remove from further competition those applications judged to be noncompetitive for award and will notify the applicant and the institutional business official. Those applications judged to be competitive for award will be further reviewed for scientific and technical merit by an appropriate review committee convened by the Division of Extramural Activities, NIAID. A second level of review will be provided by the NIAID and NIDDK Councils. Factors to be considered in the evaluation of each application will be similar to those used in review of traditional research grant applications and, in addition, will include those addressing overall proposed collaboration. INQUIRIES Written and telephone requests for the RFA and the opportunity to clarify any issues or questions from potential applicants are welcome. It is essential that prospective applicants obtain a copy of the RFA and the Special Instructions for Preparing Applications for IRPGs before preparing an application. Direct requests for the RFA and inquiries regarding scientific issues or responsiveness to: Dr. Sandra Bridges Developmental Therapeutics Branch National Institute of Allergy and Infectious Diseases Solar Building, Room 2C12 Bethesda, MD 20892 Telephone: (301) 496-8197 Dr. Ralph Bain Division of Kidney, Urologic, and Hematologic Diseases National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 3A05 Bethesda, MD 20892 Telephone: (301) 594-7556 Address the letter of intent and questions regarding review of applications to: Dr. Dianne Tingley Scientific Review Program National Institute of Allergy and Infectious Diseases Solar Building, Room 4C16 Bethesda, MD 20892 Telephone: (301) 496-0818 Direct inquiries regarding fiscal matters to: Ms. Jane Unsworth Grants Management Branch National Institute of Allergy and Infectious Diseases Solar Building, Room 4B22 Bethesda, MD 20892 Telephone: (301) 496-7075 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance, 93.856 - Microbiology and Infectious Diseases Research and 93.855 - Immunology, Allergy and Transplantation Research. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR Part 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. $$R4 END ************************************************************ ERRATUM $$E1 BEGIN R2 19930618 APPEND RFA AI-93-014 BOTH *********************** CENTERS FOR AIDS RESEARCH/CORE SUPPORT GRANT (CFAR/CSG) NIH GUIDE, Volume 22, Number 28, August 6, 1993 RFA: AI-93-014 P.T. 34; K.W. 0715008, 0710030, 0404000, 0745027, 0411005 National Institute of Allergy and Infectious Diseases National Institute of Mental Health Application Receipt Date: September 17, 1993 The following modifications are made to Request for Applications (RFA) AI-93-014, that appeared in the NIH Guide for Grants and Contracts, Vol. 22, No. 22, June 18, 1993. Under the section RESEARCH OBJECTIVES, third paragraph, and item 4 under REVIEW CONSIDERATIONS, it states that "the CFAR Director should currently be a Principal Investigator of one or more peer-reviewed, AIDS or AIDS-related research projects in the CFAR Funded Research Base". This qualification is amended to state that: The CFAR Director should be a recognized leader in the field of AIDS or AIDS-related research. Such leadership can be demonstrated by a combination of AIDS or AIDS-related research activities as exemplified by the following: currently be a Principal Investigator or Co-principal Investigator of one or more peer-reviewed, AIDS or AIDS-related research projects in the CFAR Funded Research Base; membership on AIDS or AIDS-related research study sections or ad hoc review committees; editor of a peer-reviewed AIDS or AIDS-related scientific journal; organizer of national or international meetings in the field of AIDS or AIDS-related research; or author on key scientific publications in the field of AIDS or AIDS-related research. The schedule shown in the NIH Guide, June 18, 1993 is amended: Letter of Intent Receipt Date: July 23, 1993 Final Date for Receipt of Application: September 17, 1993 Under the section Goals and Objectives of the Centers for AIDS Research, o Basic Science Cores - the following additional examples are made to the examples of Basic Science Cores that may be supported by the National Institute of Mental Health: Basic Behavioral Theory relevant to HIV Risk Behavior Initiation, Maintenance and Change; Community and Individual Sampling, Measurement and Assessment; Conceptual and Methodological Model Development for High Risk Behavior; Cultural Diversity; Multiple Informant Strategies to Supplement Self Report; Alternatives to Linear Additive Models; and Generalizability of Validity of Measures Across Subgroups. INQUIRIES Inquiries regarding scientific or programmatic issues may be directed to: Dr. Robert H. Bassin or Dr. Janet M. Young Division of AIDS National Institute of Allergy and Infectious Diseases 6003 Executive Boulevard, Room 2B31 (or 2B28) Bethesda, MD 20892 Telephone: (301) 402-0755 FAX: (301) 480-5703 Inquiries regarding fiscal matters may be addressed to: Ms. Jane Unsworth Division of Extramural Activities National Institute of Allergy and Infectious Diseases 6003 Executive Boulevard, Room 4B22 Bethesda, MD 20892 Telephone: (301) 496-7075 FAX: (301) 480-3780 $$E1 END ************************************************************ From owner-sci-resources@net.bio.net Thu Aug 05 23:00:00 1993 Path: biosci!net.bio.net From: kristoff@net.bio.net (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 22, no. 28, pt. 2, 6 August 1993 Message-ID: Date: 6 Aug 93 03:24:53 GMT Sender: kristoff@net.bio.net Lines: 1038 Approved: biosci-moderator@net.bio.net $$XID RFA HD94006 HD-94-006 P1O1 *************************************** HUMAN FETAL TISSUE CHARACTERIZATION FOR TRANSPLANTATION NIH GUIDE, Volume 22, Number 28, August 6, 1993 RFA: HD-94-006 P.T. 34; K.W. 0705035, 0745065, 0780005 National Institute of Child Health and Human Development National Institute of Diabetes and Digestive and Kidney Diseases National Institute of Neurological Disorders and Stroke Letter of Intent Receipt Date: October 1, 1993 Application Receipt Date: November 19, 1993 PURPOSE This Request for Applications (RFA) has been developed to encourage research on the standards and methods for identifying and characterizing optimal human fetal tissue for use in transplantation therapy. Joint funding by the National Institute of Child Health and Human Development (NICHD), the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and the National Institute of Neurological Disorders and Stroke (NINDS) reflects the extent of interest in evaluating human fetal tissues and their biological potentials. Attention should be given to proper collection, processing, culturing and preserving these tissues to ensure highest quality control. This research should consider addressing methods for acquisition, handling, and processing, establishing morphologic status, determining developmental age and viability, assessing sterility and genetic normality, preserving by cryopreservation, storing and establishing cell lines. President Clinton's directive of January 22 ended the moratorium on Federal funding for use of fetal tissue from induced abortions in human transplantation research. Therefore, human fetal tissues studied under this solicitation may be derived from spontaneous abortion, ectopic pregnancy, or induced abortion. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This RFA, Human Fetal Tissue Characterization for Transplantation, is related to the priority areas of maternal and infant health, and diabetes and chronic disabling conditions. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1), through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories and units of state or local governments. Applications from investigators who are minority individuals and women are encouraged. MECHANISM OF SUPPORT This RFA will use the National Institutes of Health (NIH) research project grant (R01). Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. The total project period for applications submitted in response to the present RFA may not exceed four years. The anticipated award date is July 1, 1994. This RFA is a one time solicitation. Future unsolicited competing continuation applications will compete with all investigator-initiated applications and be reviewed according to the customary peer review procedures. FUNDS AVAILABLE It is anticipated that up to six grants will be awarded under this program, contingent upon receipt of a sufficient number of meritorious applications and the availability of funds. To support these awards, $1,000,000 has been set aside for the direct costs in the first year. The duration of these awards is to be four years and the annual direct costs for the first year are not to exceed $160,000. This announcement is for a single competition with the application receipt deadline of November 19, 1993. Should there be a sufficient continuing program need, this RFA may be reissued. RESEARCH OBJECTIVES Background The use of human fetal tissue transplants has been advocated for several years as a means of treating a number of devastating diseases. Fetal tissue transplants may allow replacement of tissues and cell products that have been damaged, destroyed, or that never developed properly due to disease or a genetic disorder. These maladies are life threatening unless intervention is instituted. Childhood diseases such as inborn errors of metabolism, immune deficiencies and other entities are being considered for very early treatment using fetus-to-fetus transplants. Diseases such as insulin-dependent diabetes mellitus (IDDM) and Parkinson's Disease are also prospective candidates for transplantation therapy. The results of the Diabetes Control and Complications Trial demonstrate the profound importance of glucose control in the prevention of diabetic complications. Thus, transplantation therapy offers new avenues for tighter glucose control in IDDM patients. Initial results of surgical transplantation in Parkinson's Disease for a small number of cases hold considerable promise although more definitive study and evaluation are required. There is currently considerable interest in the therapeutic use of fetal tissues for the treatment of incurable and chronic diseases, both from the medical and the basic science community. Methods should be considered to optimize and standardize the handling and processing of fetal tissues as well as their preservation and storage. It is evident that better characterization of these more immature fetal tissues is required to assure optimal therapeutic results. Improved knowledge of the potential of these cells will define their roles in normal developmental processes based on their developmental age and biological potential, and will improve their usefulness in replacement therapy. Tissue Collection Appropriate collaboration with clinicians will be required to obtain necessary tissue in a timely fashion and collected in a manner suitable for the scheduled tissue processing. Accurate assessment of developmental age, gross examination of tissues, and grading of tissues for viability will also require a pathology/teratology assessment. In obtaining medical histories and serological screening of contributors of the products of conception for this research, appropriate informed consent must be obtained. Evaluation of pathogenic contaminants, cytogenetic studies and assessment of genetic mutations in at-risk specimens are research areas to be included. Applicants should be able to demonstrate immunologic and transplantation expertise and have available established tissue culture facilities with the expertise for growing, characterizing, cryopreserving and maintaining suitable fetal cell lines. Data Collection The data from these studies should be used to address the quality and efficacy of the tissues under investigation for transplantation therapy. This information should be applicable to the establishment of protocols and tissue processing innovations. SPECIAL REQUIREMENTS The fetal tissue acquisition and handling must comply with the regulations for Federal Funding of Fetal Tissue Transplantation Research as set forth in the NIH Guide for Grants and Contracts, Volume 22, Number 11, March 19, 1993. It is expected that at least two meetings per year in the Washington, DC area of the awardees, NIH staff, and NIH consultants, during both the first and subsequent years, will be required to assess progress and workscope. These meetings will be of benefit to the grantees and will allow them to address unforeseen difficulties, establish collaborative efforts and assess the schedule of progress. The grantees will retain primary authority and responsibility for the work. Funds for this travel should be requested in the application. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy is that applicants for NIH clinical research grants and cooperative agreements will be required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder or condition under study; special emphasis should be placed on the need for inclusion of minorities and women in studies of diseases, disorders and conditions which disproportionately affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear compelling rationale should be provided. The composition of the proposed study population must be described in terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues should be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information should be included in the form PHS 398 in Sections 1-4 of the Research Plan AND summarized in Section 5, Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations (i.e., Native Americans (including American Indians or Alaskan Natives), Asian/Pacific Islanders, Blacks, Hispanics). The rationale for studies on single minority population groups should be provided. For the purpose of this policy, clinical research includes human biomedical and behavioral studies of etiology, epidemiology, prevention (and preventive strategies), diagnosis, or treatment of diseases, disorders or conditions, including but not limited to clinical trials. The usual NIH policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are excluded. However, every effort should be made to include human tissues from women and racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. For foreign awards, the policy on inclusion of women applies fully; since the definition of minority differs in other countries, the applicant must discuss the relevance of research involving foreign population groups to the United States' populations, including minorities. If the required information is not contained within the application, the application will be returned. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and will be reflected in assigning the priority score to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. LETTER OF INTENT Prospective applicants are asked to submit, by October 1, 1993, a letter of intent that includes a descriptive title of the proposed research; the name, address, and telephone number of the Principal Investigator; the identities of other key personnel and participating institutions; and the number and title of the RFA in response to which the application may be submitted. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, the information that it contains is helpful in planning for the review of applications. It allows NICHD, NIDDK, and NINDS staff to estimate the potential review workload and to avoid conflict of interest in the review. The letter of intent is to be sent to Dr. Delbert H. Dayton at the address listed under INQUIRIES. APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 9/91) is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research and from the Office of Grants Information, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone (301) 594-7248. The RFA label available in the PHS 398 application form must be affixed to the bottom of the face page. Failure to use this label could result in delayed processing of an application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2a of the face page of the application form and the YES box checked. The title can be abridged to "Human Fetal Tissues." Submit a signed, typewritten original of the application, including the Checklist, and three signed, exact photocopies, in one package to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** At the time of submission, two additional copies of the application must also be sent to: Susan Streufert, Ph.D. Division of Scientific Review National Institute of Child Health and Human Development 6100 Executive Boulevard, Room 5E03 Bethesda, MD 20892 REVIEW CONSIDERATIONS Applications will be received by the NIH Division of Research Grants and reviewed for completeness. Incomplete applications will be returned to the applicant. NICHD, NIDDK, and NINDS staff will review the applications for responsiveness to the RFA. Applications judged to be nonresponsive will be returned. Responsive applications may be subjected to a triage by a peer-review group to determine the scientific merit relative to the other applications received in response to this RFA. NICHD will withdraw from competition those applications judged to be noncompetitive and will notify the applicant and institutional official. Those applications judged to be competitive will be further evaluated for scientific and technical merit by a review group convened solely for this purpose by the Division of Scientific Review, NICHD. Following review by the Initial Review Group, applications will be evaluated by the appropriate National Advisory Council for program relevance and policy issues before awards for meritorious applications are made. Review Criteria Applications must contain sufficient information for scientific review based on the following criteria: o Quality of proposed research to determine the optimal methods of tissue evaluation, processing, cryopreservation, maintenance, storage, tissue/cell culturing and quality control for establishment of viable, functional tissue/cells for transplantation o Demonstrated experience of the principal investigator and proposed staff relevant to this RFA, especially in the areas of immunologic and transplantation expertise, pathology/teratology and tissue preparation techniques o Adequacy of access to fetal tissue and confirmed cooperation of the professional clinical obstetric community o Plans for tissue collection to assure a broad population base, maximum access and ascertainment, rapid transport, and support of cooperating institutions o Adequacy of physical facilities for proposed studies o Quality of data analysis systems AWARD CRITERIA Responsiveness to the RFA, scientific merit, and technical proficiency, as described in the application, will be the predominant criteria for determining funding. INQUIRIES Written and telephone inquiries concerning this RFA are encouraged to clarify any issues or questions from potential applicants. Direct inquiries regarding programmatic issues, and address the letter of intent to: Delbert H. Dayton, M.D. Center for Research for Mothers and Children National Institute of Child Health and Human Development 6100 Executive Boulevard, Room 4B01 Bethesda, MD 20892 Telephone: (301) 496-5541 Joan T. Harmon, Ph.D. Division of Diabetes, Endocrinology and Metabolic Diseases National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 622 Bethesda, MD 20892 Telephone: (301) 594-7565 Eugene J. Oliver, Ph.D. Division of Demyelinating, Atrophic, and Dementing Disorders National Institute of Neurological Disorders and Stroke Federal Building, Room 806 7550 Wisconsin Avenue Bethesda, MD 20892 Telephone: (301) 496-1431 Direct inquiries regarding fiscal matters to: Ms. Mary Ellen Colvin Office of Grants and Contracts National Institute of Child Health and Human Development 6100 Executive Boulevard, Room 8A17 Bethesda, MD 20892 Telephone: (301) 496-1303 Ms. Betty E. Bailey Division of Extramural Activities National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 649 Bethesda, MD 20892 Telephone: (301) 594-7543 Mr. George Tucker Division of Extramural Activities National Institute of Neurological Disorders and Stroke Federal Building, Room 1004 7550 Wisconsin Avenue Bethesda, MD 20892 Telephone: (301) 496-9231 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance Nos. 93.847, 93.853, 93.854, and 93.865. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. $$XID RFA AI93012 AI-93-012 P1O1 *************************************** IMMUNE RECONSTITUTION OF HIV-INFECTED INDIVIDUALS (IRPG) NIH GUIDE, Volume 22, Number 28, August 6, 1993 RFA: AI-93-012 P.T. 34; K.W. 0715008, 0710070, 0705040, 0740012, 0745032 National Institute of Allergy and Infectious Diseases National Institute of Diabetes and Digestive and Kidney Diseases Letter of Intent Receipt Date: October 27, 1993 Application Receipt Date: December 8, 1993 PURPOSE The National Institute of Allergy and Infectious Diseases (NIAID) and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) invite Interactive Research Project Grant (IRPG) applications for collaborative research efforts that combine immune reconstitution and gene-based strategies to develop new treatment modalities for HIV-1 infection. The NIAID and NIDDK wish to promote research on: interactions of the Human Immunodeficiency Virus-1 (HIV-1) with the immune system that may impact on the immunologic reconstitution of infected individuals; cytokines to facilitate stem cell reconstitution of HIV-infected individuals or ameliorate/reverse HIV-related damage to the immune system; and gene-based strategies to counteract detrimental effects of HIV-1 on the immune system, to prevent infection of stem cells transplanted into HIV-infected individuals, and to improve the characteristics of ex vivo expanded lymphocytes to enable them to function more effectively in vivo. Although clinical trials will not be supported under this Request for Applications (RFA), the basic and preclinical research accomplished is expected to lay the foundation for future clinical trials. The NIAID and NIDDK request the coordinated submission of related individual research project grant applications from investigators who wish to collaborate on research, but do not require extensive shared physical resources. These applications must share a common theme and describe the objectives and scientific importance of the interchange of ideas, data, and materials among the collaborating investigators. This collaborative research will be supported by investigator-initiated Interactive Research Project Grant (IRPG) awards. For further information, potential applicants should refer to the document, Special Instructions for Preparing Applications for Interactive Research Project Grants. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This RFA, Immune Reconstitution of HIV-Infected Individuals, is related to the priority area of HIV infection. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign, for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Applications from minority individuals and women are encouraged. Applicants for IRPGs may not concurrently submit additional R01 applications (either investigator-initiated or in response to another RFA) that represent significant duplications of the efforts described in the IRPG application. Concurrent submission of program project (P01) or cooperative agreement (U01) applications that request support for essentially similar work is also prohibited. MECHANISM OF SUPPORT The support mechanism for this RFA will be the individual research project grant (R01) from investigators who wish to collaborate on research efforts directed at the development of treatment strategies utilizing immune reconstitution. The independent research projects will be organized into an IRPG that must consist of a minimum of two independent R01 applications. For this RFA, each IRPG group submission should include at least one application proposing research on stem cell or somatic cell therapies and one application proposing gene-based therapeutic strategies. Each application must clearly identify the research that will be carried out independently and that which will be carried out collaboratively and include a succinct description of the scientific relationships among the investigators and plans for collaboration, interaction, and communication. Refer to the document, Special Instructions for the Preparation of Applications for Interactive Research Project Grants. An IRPG Coordinator should be identified from among the participating R01 Principal Investigators. Since the Coordinator will be responsible for facilitating communication and collaboration among the investigators, he/she may request a modest amount of funds for an administrative core to support the time and effort contributed to these activities. See additional instructions on preparation of a IRPG application. All applicable PHS and NIH grants policies will apply to applications received in response to this RFA. Because the nature and scope of the research proposed in response to this RFA may vary, it is anticipated that the size of the awards will vary also. The budget request for the initial year's total costs (direct and indirect) for the R01 applications in the IRPG group may not exceed an average of $250,000 per R01 application. (For example, one application that requests $350,000 might be combined with two applications requesting $200,000.) Any budgets in excess of this amount must be approved by the NIAID prior to submission of the IRPG application. Requests for expensive equipment are not encouraged. Up to four years of support may be requested. Reissuance of this RFA is anticipated but not certain. If by the end of the third year, the NIAID has not announced its intent to re-advertise this RFA, incumbents should prepare unsolicited competing continuation R01 or IRPG applications that will compete with all investigator-initiated applications and will be reviewed by traditional peer review procedures. Those Principal Investigators who wish to continue collaborative efforts should consult NIAID staff before preparing their applications. FUNDS AVAILABLE The NIAID and NIDDK anticipate awarding two to four IRPGs (a total of six to eight R01 awards), for a total cost of $1.9 million for the initial year of funding. The NIAID has set aside $1.2 million for applications received in response to this RFA, and the NIDDK has set aside $0.7 million for this purpose. These funding levels are dependent on the receipt of a sufficient number of applications of high scientific merit. RESEARCH OBJECTIVES Background The mortality and morbidity suffered by HIV-infected individuals is primarily the consequence of immune deficits that become increasingly more severe during the course of the disease. Several immune-based strategies are presently under evaluation for ameliorating and/or reversing immune deficiencies in HIV-infected individuals. Prominent among these are the use of HIV envelope vaccines or therapeutics (e.g., interleukin-2) to augment existing responses to the virus or enhance the immune system as a whole; HIV-specific lymphocytes or antibodies to supplement the response elicited during the natural course of infection; and bone marrow transplantation (BMT) to restore immune cells lost as a result of HIV-1 infection. BMT is currently being used to restore marrow function in cancer patients whose hematopoietic systems have been ablated by chemo- and radiation therapy. The immediate goal is the reconstitution of hematopoietic lineages required for acute survival, i.e., myeloid and megakaryocyte lineages. Less attention has been paid to the restoration of the lymphoid lineage despite the fact that infectious disease is responsible for a significant portion of the mortality in survivors of BMT. The CD4/CD8 T lymphocyte ratio may remain abnormal for prolonged periods after transplantation, and persistent functional deficits are evidenced by various in vitro assays of immune function. Basic information that bears on the feasibility of immune reconstitution as a therapeutic approach for HIV infection is currently incomplete. For example, it is not known with certainty whether or not human multipotent stem cells can be infected by HIV-1 and whether an HIV-1-infected host can provide the proper physiological environment for the maturation of stem cells to their respective differentiated lineages. Further, it is not clear whether a source of stem cells can be identified that meets the minimal criteria for the success of a gene therapy utilizing stem cells, namely the capacity to be maintained in vitro; to be modified to resist HIV-1 infection; to home, differentiate and expand in vivo after modification; and to retain the HIV-resistant phenotype in differentiated lineages, particularly in T lymphocytes. Human and animal model studies are currently assessing the capability of CD34+ bone marrow cells to reconstitute a functional hematopoietic system in appropriately conditioned recipients. Other potential sources of multipotent stem cells have been identified, including fetal liver, yolk sac, and cord blood. There is increasing evidence to support the hypothesis that very primitive stem cells may possess characteristics favorable to engraftment in a nonautologous setting such that they may be able to persist without eliciting either a graft versus host reaction or a host versus graft reaction. Further research is needed to confirm and amplify these findings. Alternatively, the immune system might be temporarily supported in the face of disease-related immunodeficiency by the transfer of antigen-specific, ex vivo expanded lymphocytes. Recent clinical trials suggest that bone marrow transplant patients at risk of cytomegalovirus-related disease might benefit from adoptive immunotherapy with cytotoxic T cells that are capable of killing virus-infected cells. Animal and human studies are exploring a possible role for HIV-specific T cells in controlling the infection. Therefore, research on therapies that utilize cells with limited capacity for in vivo expansion will be supported under this RFA because of their potential utility in controlling HIV-1 in early stage disease and in combatting opportunistic infections. Goals and Objectives The long term goal of this RFA is to provide an experimental basis for using immune reconstitution as a therapy in individuals whose immune systems are compromised by infectious disease. This RFA focuses on HIV/AIDS for which there is need for therapies that can maintain/supplement the immune systems of infected individuals. Since it is unlikely that HIV-1 can be totally eradicated from the body by means presently available, strategies for the immune reconstitution of HIV-infected individuals will require that the transferred cells be genetically engineered to resist infection by, and/or the damaging effects of, HIV-1. Efforts are currently underway to use gene-based strategies and immune reconstitution as independent modalities to treat HIV-1 and associated infections. The objective of this RFA is to encourage preclinical research that combines the two approaches through collaborative efforts among independent investigators. Research Scope Research responsive to this RFA includes, but is not limited to, the following: Research to clarify interactions of HIV with the immune system that may bear on the successful reconstitution of infected individuals o Mechanism(s) of destruction of lymphoid tissue by HIV-1 and gene-based strategies for blocking mediators responsible for the damage. o Effects of HIV infection on thymopoiesis and multilineage engraftment of stem cells and gene-based strategies to counter detrimental effects. o Aberrant T lymphocyte homeostasis in HIV-infected individuals or in relevant animal models and gene-based therapies to normalize the CD4/CD8 ratio. o Abnormal regulation of cytokine gene expression and gene- based strategies for ameliorating the dysfunction of the cytokine network in HIV-infected individuals. Research on antiviral strategies o Design and evaluation of new gene-based antiviral strategies to be used in stem cells or other sources of immune cells. o Effects of specific antiviral strategies on the biological program of engineered multipotent stem cells. o Antiviral gene expression during differentiation of engineered stem cells in vitro and in vivo. o Isolation, modification, and testing of antigen-specific, in vitro expanded lymphocytes. Modification includes the use of genetic engineering to improve the potency, specificity, or other characteristics of the cells to enable them to function more effectively in vivo. Developmental research o Development of novel sources of multipotent stem cells that can be maintained in vitro and modified by genetic engineering techniques to resist subsequent HIV infection and that are capable of differentiating in vivo and retaining the HIV resistant phenotype in the differentiated lineages. Information bearing on the transplantability of multipotent stem cells across allo- and xeno-histocompatibility barriers is needed. o Discovery and characterization of cytokines, growth and/or differentiation factors, particularly those capable of interacting with T cell progenitors or their immediate antecedents. The discovery and development of new soluble factors are needed for the in vitro maintenance of target cells for genetic engineering, to provide sufficient material for evaluating the success and impact of experimental anti-HIV strategies at an early point, and to stimulate in vivo expansion of engineered stem cells. o Development of an in vitro colony forming assay for T cell progenitors similar to those already in use for other hematopoietic cell progenitors. Existing methodologies for quantifying T cell progenitor cells are time and labor intensive and measure progenitors indirectly by quantifying their ability to repopulate the thymus in animal models or to respond to mitogens in vitro. While it is anticipated that complete development of new strategy for immune reconstitution will not occur within the project period for all groups, a rationale for the most likely use of discoveries made or an outline of a plan for eventual clinical trials should be included. Restrictions and Exclusions Clinical trials will not be supported under this RFA. However, proposed analysis of samples acquired from NIAID-sponsored clinical trials is appropriate. Samples from ongoing trials may be made available for specific experiments. Budgetary limitations will prohibit extensive use of primates in these projects (see MECHANISM OF SUPPORT). If a therapeutic strategy is developed to an advanced stage under the RFA, every effort will be made to provide testing through NIAID-supported primate resources. SPECIAL CHARACTERISTICS Meetings Effective communication among IRPG investigators is very important. IRPG investigators should plan to participate in one meeting per year to be held alone or in conjunction with an NIAID-sponsored meeting such as the National Cooperative Drug Discovery Group (NCDDG) meeting. Funds to support attendance at the meeting should be included in each PI's budget. Patent Coverage Inasmuch as the development of effective treatment strategies is the objective of this effort and since the active involvement by industrial laboratories is facilitated by the existence of adequate patent coverage, it is essential that applicants provide a plan, agreed upon by the group, for obtaining patent coverage and for licensing where appropriate. In the event that the need for patent coverage is anticipated, the grantee should contact program staff listed under INQUIRIES well in advance of the application submission deadline, who will provide the details of the patent requirements and relevant regulations. The NIAID will not be a partner in any patents or royalties ensuing from this research. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy is that applicants for NIH clinical research grants and cooperative agreements are required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder or condition under study; special emphasis should be placed on the need for inclusion of minorities and women in studies of diseases, disorders and conditions which disproportionately affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear compelling rationale must be provided. The composition of the proposed study population must be described in terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues should be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information must be included in the form PHS 398 in Items 1-4 of the Research Plan AND summarized in Section 5, Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations [i.e., Native Americans (including American Indians or Alaskan Natives), Asian/Pacific Islanders, African Americans, Hispanics]. The rationale for studies on single minority population groups must be provided. For the purpose of this policy, clinical research is defined as human biomedical and behavioral studies of etiology, epidemiology, prevention (and preventive strategies), diagnosis, or treatment of diseases, disorders or conditions, including but not limited to clinical trials. The usual NIH policies concerning research involving human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are excluded. Every effort should be made to include tissues from women and racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. For foreign awards, the policy on inclusion of women applies fully; since the definition of minority differs in other countries, the applicant must discuss the relevance of research involving foreign population groups to the United States' populations, including minorities. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in the study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and will be reflected in assigning the priority score to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. NOTE: Peer review groups need adequate information about the composition of proposed study populations in all applications involving human subjects. To avoid delays in review of such applications, the NIAID therefore requires that, as a minimum, the application must contain demographic data about the clinic and/or in-patient population from which study subjects (including clinical samples, materials, or fluids) will be drawn: average hospital admissions and/or clinic visits per year; percentage distribution of black/hispanic/other minority/non-minority populations; gender; etc. Studies using non-hospital populations, such as community-based studies, should provide similar data about populations in the area or region from which the study subjects will be drawn. In the absence of current data, historical demographic information and/or previous recruitment data for similar studies from the proposed study sites should be provided. LETTER OF INTENT Prospective applicants are asked to submit, by October 27, 1993, a letter of intent that includes descriptive titles of each proposed research project in the IRPG group, the names and address of the Principal Investigators and other key personnel, the participating institutions, and the number and title of this RFA. Although a letter of intent is not required, is not binding, and does not enter into the review of the application, the information that it contains is helpful in planning for the review of expected applications. It allows NIAID staff to estimate the potential workload for reviewers and to avoid possible conflict of interest in the review process. The letter of intent is to be sent to Dr. Dianne Tingley at the address listed under INQUIRIES. APPLICATION PROCEDURES Since applications that do not address the objectives of this RFA will be considered nonresponsive and will be returned without review, potential applicants are strongly encouraged to discuss their research plans with program staff before completing their applications. Applications are to be submitted on the grant application form PHS 398 (rev. 9/91). These forms are available at most institutional offices of sponsored research and from the Office of Grants Information, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone (301) 594-7248. The RFA label available in the PHS 398 application kit must be affixed to the bottom of the face page of the application. To assure the identification of your application with this RFA, the "Yes" box must be marked in item 2a of the face page of the application and the RFA number (RFA AI-93-012) and title IMMUNE RECONSTITUTION OF HIV-1 INFECTED INDIVIDUALS (IRPG) entered in the provided spaces in item 2a. See the attached special instructions for further information on application procedures. The R01 applications constituting the proposed IRPG group must be submitted in a single package, whether or not the applications originate from the same institution. Each application in the package must be clearly identified and a cover letter must list the total number of applications submitted for the IRPG, indicating the Principal Investigator and title of each. The various applications should not be paginated or collated together like a Program Project, since each R01 application will be processed individually and assigned its own grant number by DRG, NIH. For each application, the original, three copies, and the appendix material must be put together in one bundle and clearly identified. Failure to follow the instructions regarding submission date and packaging may lead to a delay in review. The IRPG package must be sent or delivered to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** At the time of submission to the Division of Research Grants (DRG), also submit two additional exact copies of the IRPG applications including appendices directly to Dr. Dianne Tingley at the address listed under INQUIRIES. REVIEW CONSIDERATIONS Applications that have not followed the instructions for preparation or that do not conform to the instructions contained in the PHS 398 (rev. 9/91) application kit will be judged incomplete and will be returned to the applicant. Each R01 application will be reviewed by DRG staff for completeness and by NIAID and NIDDK staff to determine responsiveness to this RFA; those individual or group applications judged to be incomplete or non-responsive will be returned to the applicant without review. To be considered responsive, the application should be directed towards the attainment of the stated programmatic goals (RESEARCH OBJECTIVES). Those applications that are complete and responsive may be subjected to a triage before or during the initial scientific peer review by a peer review group convened by the Division of Extramural Activities (DEA), NIAID to determine their scientific merit relative to the other applications received in response to this RFA. The NIAID will remove from further competition those applications judged to be noncompetitive for award and will notify the applicant and institutional business official. Those applications judged to be competitive for award will be further reviewed for scientific and technical merit by a review committee convened by the Scientific Review Program, DEA, NIAID. A second level of review will be provided by the National Advisory Allergy and Infectious Diseases Council and the National Diabetes and Digestive and Kidney Diseases Advisory Council. In the event of several highly qualified applications, final funding recommendations will be based on Program priorities. Review Criteria The factors considered in evaluating the scientific merit of each application will be: o Scientific and technical merit of each individual R01 application, including originality and feasibility of the approach; o Appropriateness and adequacy of the experimental approach and methodology proposed to carry out the research; o Adequacy of plans for collaboration and communication with other investigators in the IRPG group; o Adequacy of resources and environment (e.g., facilities and equipment, shared interactive resources [cores]); o Experience, training, time commitment, and qualifications of the investigators (a commitment of at least 15 percent is recommended for Principal Investigators). Review Procedures Each R01 application will be reviewed independently for scientific and technical merit. Reviewers will read section 7 and will assess the intended collaborations just as they do the proposed collaborations in any other types of applications. As appropriate, the effectiveness and merit of the collaborations may contribute to the overall assessment of the application. In addition, budget recommendations related to the appropriateness of shared interactive resources (cores) will be reviewed for each application. Recommendations concerning core(s) in an application will be documented in administrative notes in the summary statements. These notes will assist the NIAID and NIDDK in making final decisions on each application in the context of the overall IRPG. AWARD CRITERIA The NIAID and NIDDK anticipate awarding two to four IRPG groups (six to eight R01 awards total) as a result of this RFA. The final number and specific amounts of awards to be made will depend upon consideration of the following: o Results of the initial scientific and technical merit review; o Potential contribution of the proposed research to the goals and objectives of the RFA; o Program balance; o Availability of resources. INQUIRIES It is essential that prospective applicants carefully review the RFA and the Special Insturctions for Preparing Applications for IRPGs (available from program staff listed below). NIAID and NIDDK staff welcome the opportunity to clarify issues or answer questions from potential applicants. Direct inquiries regarding scientific issues or responsiveness to: Dr. Sandra Bridges Division of AIDS National Institute of Allergy and Infectious Diseases Solar Building, Room 2C12 Bethesda, MD 20892 Telephone: (301) 496-8197 Dr. Ralph Bain Division of Kidney, Urologic, and Hematologic Diseases National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 3A05 Bethesda, MD 20892 Telephone: (301) 594-7556 Direct inquiries regarding the scientific review process, format of applications, and address the letter of intent to: Dr. Dianne Tingley Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Building, Room 4C16 Bethesda, MD 20892 Telephone: (301) 496-0818 Direct inquiries regarding fiscal matters and the format of applications to: Ms. Jane Unsworth Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Building, Room 4B22 Bethesda, MD 20892 Telephone: (301) 496-7075 Applicants who wish to use express mail or a courier service are advised to follow the carrier's requirements for showing a street address. The address for the Solar Building is: 6003 Executive Boulevard, Rockville, MD 20852 Schedule Letter of Intent Receipt Date: October 27, 1993 Application Receipt Date: December 8, 1993 Scientific Review Date: March 1994 Advisory Council Date: June 1994 Earliest Award Date: July 1994 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance, 93.856 - Microbiology and Infectious Diseases Research and 93.855 - Immunology, Allergy and Transplantation Research. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR Part 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. From owner-sci-resources@net.bio.net Thu Aug 05 23:00:00 1993 Path: biosci!net.bio.net From: kristoff@net.bio.net (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 22, no. 28, pt. 3, 6 August 1993 Message-ID: Date: 6 Aug 93 03:25:42 GMT Sender: kristoff@net.bio.net Lines: 956 Approved: biosci-moderator@net.bio.net $$XID RFA CA93037 CA-93-037 P1O1 *************************************** ROLE OF THE MICROENVIRONMENT IN BREAST AND PROSTATE CANCER NIH GUIDE, Volume 22, Number 28, August 6, 1993 RFA: CA-93-037 P.T. 34; K.W. 0715036, 1002004, 1002008, 0760025 National Cancer Institute Letter of Intent Receipt Date: September 10, 1993 Application Receipt Date: November 23, 1993 PURPOSE The Cancer Biology Branch, Division of Cancer Biology, Diagnosis and Centers (DCBDC) at the National Cancer institute (NCI), in collaboration with the Chemical and Physical Carcinogenesis Branch, Division of Cancer Etiology (DCE), NCI, invites investigator- initiated research project grant applications to elucidate the molecular interactions among the cell populations of human breast and prostatic cancer that contribute to malignant progression. New and experienced investigators in relevant fields and disciplines may apply for funds to pursue this research. Breast and prostate tissues have a number of characteristics in common; e.g., steroidal sex hormones modulate the growth and differentiation observed during normal neonatal development and at puberty; these same hormones are implicated in the growth of malignancies of each organ; and hormonal intervention remains a key component of treatment of both breast and prostate cancer in patients. In addition, some association between the two neoplasms is suggested by epidemiological data of an increased risk of prostate cancer among relatives of women with breast cancer, as well as a significant increased risk of breast cancer in families with prostate cancer. It is clear that effects of the steroidal hormones on the epithelium are mediated indirectly by interactions with stroma during normal development and differentiation in both organs. Epithelial-stromal interactions may also be influenced by other hormones and growth factors. More importantly, there is good evidence to indicate that aberrations in epithelial-stromal interactions occur during the course of neoplastic progression. Stromal components that might participate in these micro-environmental influences include fibroblasts, endothelial cells, macrophages, the extracellular matrix contributed by both epithelial and stromal cells, and in the case of breast tissue, adipocytes. Little is known of the contribution of this mosaic of cells to the malignant process at the cellular or molecular level. In animal models, a number of carcinogens (naturally occurring and synthetic) have been implicated as potential transforming agents for breast and prostate tissues but virtually nothing is known about the interaction of such carcinogens with stromal components in normal or malignant breast and prostatic tissues. The aim of this Request for Applications (RFA) is to foster application of recent advances in molecular and cellular biology, using appropriate model systems, to study the effects of tumor cell-stroma interactions relevant to tumor development and progression in human breast or prostatic tissues. A multidisciplinary approach involving interactions among basic and clinical scientists is encouraged. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This RFA, Role of the Microenvironment in Breast and Prostate Cancer, is related to the priority area of cancer. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Research grant applications may be submitted by domestic and foreign for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State or local governments, and eligible agencies of the Federal government. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT Support of this RFA will be by National Institutes of Health (NIH) individual research project grants (R01). Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. The total project period for applications submitted in response to the present RFA may not exceed four years. Awards will be administered under PHS grants policy as stated in Public Health Service Grants Policy Statement, DHHS Publication No. (OASH) 90-50,000, revised October 1, 1990. The present RFA announcement is for a single solicitation with a specified deadline of November 23, 1993 for receipt of applications. The NCI anticipates making up to twelve awards for project periods of up to four years, if meritorious proposals and funds are available. The anticipated award date is July 1, 1994. Because the nature and scope of the research proposed in response to this RFA may vary, it is anticipated that the size of an award may vary also. FUNDS AVAILABLE Approximately $2,000,000 in total costs per year for up to four years will be committed to fund applications submitted in response to this RFA. It is anticipated that up to twelve awards will be made. This level of support is dependent on the receipt of a sufficient number of applications of high scientific merit. Although funds to support this program are currently provided for in the financial plans of the NCI, awards pursuant to this RFA are contingent upon the availability of funds for this purpose. RESEARCH OBJECTIVES Background The incidence of breast carcinoma increases with advancing age. About 183,000 new cases and approximately 46,000 deaths due to breast cancer are expected to occur in 1993. It is estimated that in 1993 there will be 165,000 newly diagnosed cases and 35,000 deaths due to prostate cancer. Some association between the two diseases is suggested by epidemiological data. For example, a family history of prostate cancer can have a significant effect on increasing breast cancer risk. Similarly, a significantly higher frequency of prostate cancer has been reported in relatives of breast cancer patients than in relatives of control groups. Breast and prostatic carcinomas originate in epithelial cells; however, the growth and progression of the cancer is intimately related to its microenvironment, i.e., the stroma. Studies on embryological development of the mammary gland and the prostate have indicated that hormonally-induced ductal morphogenesis and epithelial growth is mediated by the interactions between stroma and epithelia. During this neonatal development the carefully timed acquisition of steroid hormone receptors by stromal cells may be responsible for these hormonally-induced events. Studies on the hormonal regulation of differentiation of the mammary gland in vitro indicate that the presence of stromal components can determine the extent and type of functional epithelial maturation. However, the biochemical interactions and molecular communications underlying these events are poorly understood. Breast Cancer Familial clustering of breast cancer indicates that there is a genetic component predisposing individuals to breast cancer. Although it is the epithelial cell which is designated as cancerous, it has been reported that skin fibroblasts derived from breast cancer patients may also be altered and exhibit characteristics associated with a transformed and/or fetal phenotype. Furthermore, these characteristics of fibroblasts may precede the detection of breast cancer. Many growth factors including bFGF, aFGF and TGFa as well as cytokines (e.g., IL-6) may be made available to epithelial cells from the adjacent mammary stroma. Further, recent data indicate that the primary source of the epithelial mitogen IGF is the breast stroma. Analysis of fibroblasts from benign breast showed the production of IGF-I mRNA while fibroblasts from malignant lesions expressed IGF-II mRNA, suggesting a correlation with disease progression. In the mammary tissue, fibroblast stroma has been shown to produce extracellular matrix molecules such as fibronectin and tenascin that influence cell adhesion and proliferation. Tenascin is known to reduce epithelial cell adhesiveness. It is absent in normal breast, its distribution being restricted to embryonic and malignant tissues. A new gene coding for the enzyme stromelysin-3 (ST-3), has been identified, that is expressed specifically in stromal cells surrounding invasive breast carcinomas. ST-3 is a new member of the family of metalloproteinase enzymes which degrades the extracellular matrix. ST-3 is postulated to play an important role in progression of epithelial malignancies. Prostate Cancer Androgens regulate the early growth and morphogenesis of the prostatic epithelium indirectly by their effects on mesenchymal (stromal) tissues. Androgens may also induce the production of andromedins from stromal cells that influence prostatic epithelial growth by paracrine mechanisms. One major family of growth factors for prostatic epithelial cells may be the fibroblast growth factor (FGF). FGF-7, or keratinocyte growth factor, produced by the stromal cells, in the androgen-dependent Dunning rat tumor is a mitogen for those tumor cells that have FGF-7 receptors. In the more malignant androgen-independent tumors both FGF production and the tumor FGF receptor phenotype are modified. Androgen-sensitive LNCaP prostatic tumor cells will form tumors in nude mice only when the inoculum is mixed with bone- or prostate-derived fibroblasts. Other fibroblasts are not permissive for tumor growth. Differences in prostate tumor incidence in different mouse strains or in rat models may also result from characteristics of the stromal compartment. Recent observations indicate that mesenchymal or stromal inductors can impose strong control over the growth of transformed epithelial cells. Rationale for this RFA This RFA is intended to encourage a variety of investigator-initiated research projects to use appropriate model systems that take into consideration the highly interactive environment of the tumor cells, as well as the contributions of the tumor and host cells to the growth and metastatic spread of breast or prostatic carcinomas. It is also important to delineate the genetic and environmental factors involved in stromal-epithelial interactions which are relevant to malignant progression of hormonally regulated tumors. It may include collaborations among basic and clinical scientists and should embrace an array of molecular and cellular approaches. Evidence of the establishment of reliable tumor cell systems or relevant tumor models should be included in the application. Applications that propose to explore interactions of the stroma with only normal epithelium will not be considered responsive to this RFA. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy is that applicants for NIH clinical research grants and cooperative agreements are required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder or condition under study; special emphasis must be placed on the need for inclusion of minorities and women in studies of diseases, disorders and conditions which disproportionately affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear compelling rationale must be provided. The composition of the proposed study population must be described in terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues must be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information must be included in the form PHS 398 in the Research Plan, parts 1-4, AND summarized in part 5, Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations (i.e., Native Americans [including American Indians or Alaskan Natives], Asian/Pacific Islanders, Blacks, Hispanics). The rationale for studies on single minority population groups should be provided. For the purpose of this policy, clinical research is defined as human biomedical and behavioral studies of etiology, epidemiology, prevention (and preventive strategies), diagnosis, or treatment of diseases, disorders or conditions, including but not limited to clinical trials. The usual policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are exempt from this requirement. However, every effort should be made to include human tissues from racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. For foreign awards, the policy on inclusion of women applies fully; since the definition of minority differs in other countries, the applicant must discuss the relevance of research involving foreign population groups to the United States' populations, including minorities. If the required information is not contained within the application, the application will be returned. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of minorities in a study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and reflected in assigning the priority score to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. LETTER OF INTENT Prospective applicants are asked to submit, by September 10, 1993, a letter of intent that includes a descriptive title of the proposed research, the name, address, and telephone number of the Principal Investigator, the identities of other key personnel and participating institutions, and the number and title of the RFA in response to which the application may be submitted. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, the information that it contains is helpful in planning for the review of applications. It allows NCI staff to estimate the potential review workload and to avoid conflict of interest in the review. The letter of intent is to be sent to Dr. Suresh Mohla at the address listed under INQUIRIES. APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 9/91) is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research and from the Office of Grants Information, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892-9912, telephone 301/594-7248. The RFA label available in the PHS 398 application form must be affixed to the bottom of the face page of the application. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA number and title, "Role of the Microenvironment in Breast and Prostate Cancer," must be typed on line 2a of the face page of the application form and the YES box must be marked. Submit a signed, typewritten original of the application, including the Checklist, and four signed, exact, clear, single-sided photocopies, in one package with the appendices to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892-9912** At the time of submission, two additional copies of the application must also be sent to: Referral Officer Division of Extramural Activities National Cancer Institute Executive Plaza North, Room 636A Bethesda, MD 20892 Applications must be received by November 23, 1993. If an application is received after that date, it will be returned to the applicant. The Division of Research Grants (DRG) will not accept any application in response to this announcement that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. The DRG will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of substantial revisions of applications already reviewed, but such applications must include an introduction addressing the previous critique. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed by DRG staff for completeness. Incomplete applications will be returned to the applicant without further consideration. Complete applications will be evaluated by NCI program staff to determine if they are responsive to the program requirements and criteria stated in this RFA. If the application is not responsive to the RFA, NCI staff will contact the applicant to determine whether to return the application to the applicant or submit it for review in competition with unsolicited applications at the next review cycle. Applications may receive a preliminary scientific peer review (triage) by an NCI peer review group on the basis of relative competitiveness. The NIH will withdraw from further competition those applications judged to be non- competitive for award and notify the applicant Principal Investigator and institutional official. Those applications judged to be responsive and competitive will be further evaluated according to the review criteria stated below for scientific and technical merit by an appropriate peer review group convened by the Division of Extramural Activities, NCI. The second level of review by the National Cancer Advisory Board considers the special needs of the Institute and the priorities of the National Cancer Program. Review criteria for evaluating the scientific merit of this RFA will be: o extent to which the proposed research addresses the goals of the RFA o scientific and technical significance and originality of proposed research o appropriateness and adequacy of the experimental approach and methodology proposed to carry out the research, and potential relevance of the model system to human breast or prostate cancer o qualifications and research experience of the Principal Investigator and staff o demonstration of availability and access to appropriate resources necessary to perform the research o adequacy of provision for the protection of human subjects and the humane treatment of animals o adequacy of the plans for inclusion of minorities o adequacy of available facilities o appropriateness of the proposed budget and duration in relation to the proposed research AWARD CRITERIA The anticipated date of award is July 1, 1994. In addition to the technical merit of the application, NCI will consider how well the proposed research meets the goals and objectives of the program as described in the RFA. Only highly-rated projects will be funded. INQUIRIES Written and telephone inquiries concerning the objectives and scope of this RFA or inquiries about whether or not specific proposed research would be responsive are strongly encouraged and may be directed to program staff listed below. NCI program staff welcome the opportunity to clarify any issues or questions from potential applicants. Direct inquiries regarding programmatic issues, address the letter of intent to, and send two copies of the PHS 398 to: Dr. Suresh Mohla Division of Cancer Biology, Diagnosis, and Centers National Cancer Institute Executive Plaza North, Room 505 6130 Executive Boulevard Rockville, MD 20892 Telephone: (301) 496-7028 FAX: (301) 402-1037 Direct inquiries regarding fiscal and administrative matters to: Mr. Robert Hawkins Grants Management Branch National Cancer Institute Executive Plaza South, Room 243 Bethesda, MD 20892 Telephone: (301) 496-7800 ext. 13 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.396, Cancer Biology. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health $$XID RFA AI93017 AI-93-017 P1O1 *************************************** MULTICOMPONENT VACCINE DEVELOPMENT NIH GUIDE, Volume 22, Number 28, August 6, 1993 RFA: AI-93-017 P.T. 34; K.W. 0740075, 1002045, 0710070 National Institute of Allergy and Infectious Diseases Letter of Intent Receipt Date: October 1, 1993 Application Receipt Date: November 24, 1993 PURPOSE The National Institute of Allergy and Infectious Diseases (NIAID) invites applications to conduct basic research leading to the design of new innovative approaches for the synthesis and development of combination vaccines. Multicomponent (multivalent) combination vaccines containing antigens to viral and/or bacterial components provide many distinct advantages over conventional vaccines and allow for the introduction of "disease-specific", "age-specific" and "duration-specific" designer vaccines. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This Request for Applications (RFA), Multicomponent Vaccine Development, is related to the priority area of immunization and infectious diseases. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State or local governments, and eligible agencies of the Federal Government. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT Awards made under this RFA will use the National Institutes of Health (NIH) individual research project grant (R01). Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. The total project period for applications submitted by domestic institutions in response to the present RFA may not exceed four years; the total project period for applications submitted by foreign institutions may not exceed three years. The earliest possible award date is July 1, 1994. Applicants are encouraged to coordinate, through the use of consortium arrangements or subcontracts, integrated approaches with individuals or institutions having relevant reagents and expertise in their use, demonstrated ability in a particular area of relevant research, or access to relevant patient populations so as to accelerate technical progress and clinical development of promising therapies. Because the nature and scope of the research proposed in response to this RFA may vary, it is anticipated that the amounts of the awards will vary also. This RFA is a one-time solicitation. Future competing continuation applications will compete with all unsolicited investigator-initiated applications and be reviewed by an appropriate Study Section according to the customary NIH referral and peer review procedures. FUNDS AVAILABLE The estimated level of support (total direct and indirect costs) for the entire program for the first year is $1.5 million. Foreign applications that may be funded under this RFA are not eligible for indirect costs. The NIAID anticipates making a minimum of four new awards. RESEARCH OBJECTIVES Background Immunization is a principal feature of the health care of infants and young children throughout the world. Universal immunization programs, those that deliver vaccines to all children, are responsible for much of the increase in life expectancy in the last half-century. Although most infants receive their first dose of vaccine at an appropriate age, by the third dose of DTP vaccines, immunization of inner city and minority children in the U.S. is significantly delayed and they are, therefore, at risk of disease. Vaccines that would require fewer doses and could be administered orally would facilitate the immunization of all infants. The future impact of combination vaccines on immunization programs must be considered in the context of the Children's Vaccine Initiative (CVI). The ability to selectively eradicate various childhood diseases through the development of immunization programs that incorporate new emerging technologies for the creation of improved, safe and efficacious vaccines is the primary aim of the NIAID and of th