The literature on oral immunity, oral tolerance, etc. is probably one of
the most misleading in all of immunology. The first problem is the
concept that IgA is an antibody involved in protective immunity. There
are few good data to demonstrate this. Take the oral polio vaccine for
example: oral immunization invariably elicits circulating IgG as well as
local immune effector. Thus, it is not valid to conclude solely on the
basis of studies using a mucosal immunization route that local antibodies
such as sIgA-and not circulating IgG- are the mediators of protective
immunity. An oft-cited example of the superiority of local immunity to
systemic immunity is derived from the comparison of live attenuated oral
poliovirus vaccines with killed inactivated vaccines. Oral vaccine is
claimed to impart greater intestinal-and hence greater overall immunity
and there is evidence that recipients of live oral polio vaccine
subsequently challenged with live vaccine virus strains excrete less virus
in their feces compared with recipients of inactivated polio vaccines
(Ogra, P. L. 1993. Global eradication of poliomyelitis: reinvent the wheel
or use existing options effectively? Public Health Rev. 21:143-50. ).
However, the inactivated vaccine also protects against virus excretion by
the fecal route and is even more effective compared with the live vaccine
in reducing oropharyngeal excretion of live virus (Henry, J. L., E. S.
Jaikaran, J. R. Davies, A. J. Tomlinson, P. J. Mason, J. M. Barnes and A.
J. Beale. 1966. A study of polio vaccination in infancy: excretion
following challenge with live virus by children given killed or living
poliovaccine. J.Hyg (Lond). 64:105-20. and Marine, W. M., T. D. Y. Chin
and C. R. Gravelle. 1962. Limitation of fecal and pharyngeal poliovirus
excretion in Salk-vaccinated children. A family study during a type 1
poliomyelitis epidemic. Am J.Hyg. 76:173-195.). Furthermore, the
exclusive use of killed polio vaccine in the United States through 1962
reduced the incidence of polio by 90% in nonvaccinated individuals (Salk,
D. 1980. Eradication of poliomyelitis in the United States. II. Experience
with killed poliovirus vaccine. Rev. Infect. Dis. 2:243-57.), and the
exclusive use of killed vaccine in Finland, Holland, Iceland, and Sweden
eliminated circulating pathogenic polioviruses in these countries
(Bottiger, M. 1984. Long-term immunity following vaccination with killed
poliovirus vaccine in Sweden, a country with no circulating poliovirus.
Rev. Infect. Dis. 6:S548-S551. ). These results indicate that the
systemically-administered killed vaccine effectively reduces mucosal
transmission of wild-type virus. The fact that the sIgA induced by oral
poliovirus vaccines has never been documented to be the mediator of
reduced virus excretion again emphasizes the paucity of evidence that any
advantage of oral vaccination is due to elicitation of sIgA antibodies.
In addition, immunity against such mucosal pathogens as Shigella and
Vibrio cholera is correlated with serum IgG antibodies and not local IgA.
Even influenza virus, a strict pathogen of the respiratory mucosa, is
reasonably well controlled by yearly intramuscular injections that elicit
IgG antibodies. SO mucosal immunization is not needed to protect against
mucosal pathogens, but there are situations where it can be effective
because it also elicits circulating IgG.
Therefore the confusion around oral immunity and tolerance probably has
to do with which immune effectors are elicited. The route is likely only
one determinant-other determinants are the form of the antigen, the
mucosal site, etc. The IgA crowd has long neglected the reality of the
role of IgA in immunity-IgA deficiency is mostly a benign ccondition weith
a rate over 1/2 that of HIV infection in caucasians. Surely something
that common would be a bigger medical problem if in fact it were medically
significant. It isn't.
Be happy to provide you with more information.
Jerry Pier, Channing Lab, Harvard Meddical School, Boston, MA 02115
In article <3p5et7$mjo at ixnews2.ix.netcom.com>, msgold at ix.netcom.com
(Monica Ranes Goldberg) wrote:
> Can someone set me straight on conditions/antigens which induce
> tolerance when taken orally as opposed to those capable of eliciting an
> immune response? I have long understood that most antigens taken
> orally lead to tolerance (thus the basis of "feeding" MBP to EAE mice
> and thus relieving autoimmune reactions)...Of course there are
> conditions under which a "protective" response can be elicited when
> antigen is encountered orally (sabin live attenuated polio vaccine for
> example)....I had assumed the critical difference was that the polio
> vaccine was alive and thus capable of penetrating the mucosal lining
> and also capable of generating a transient infection...But now I am
> confused by a recent paper that appeared in Science (May 5,
> 1995/vol.268) regarding antigens expressed in plants. When "fed" to
> mice, IgA annd IgG specific to the cloned antigen were indeed elicited.
> There is even a News & Views article in the May 5 Science touting the
> great potential of oral vaccines grown in plants....even discussion of
> "feeding" babies "banana vaccines"...my first impression is that such
> an approach could be potentially dangerous should tolerance be induced
> instead of immunity, particularly when fed to infants....Your comments
> would be greatly appreciated!
> Monica Ranes-Goldberg, Ph.D.
> Immunology Instructor
> UC Berkeley Ext.
