Will there ever be a Vaccine to HIV?

David Peritt Peritt_d at a1.mscf.upenn.edu
Fri Mar 3 14:44:17 EST 1995


In article <3iu6iv$ndg at dns1.NMSU.Edu> Shahram Mori, smori at nmsu.edu writes:

>No matter how much the virus mutates, it has to maintain certain
antigenic
>conservativity or it would lose functionality. 

This is true.  There are determinants that if changed would destroy
protein function.  It these could be mapped then using these for vaccines
is logical.  The problem is a basic immunological phenomena.  Most
vaccine discussions do not enter the realm of MHC class I vs II
presentation.  In fact, most trials for an antibody vaccine which could
be generated with injection of a protein have failed.  I would argue that
these may fail due to the antigen being solely class II presented
(therefore CD4 cells) which help b cells to make specific antibody.  CD4
cells do have some cytotoxic activity but not compared to the
professional CD8 CTL cells.  The key to getting to the "non-mutable
proteins" which may be internal viral enzymes lies in loading class I and
therefore activating CD8 to kill infected cells.  Or if you buy Jay Levys
story these will get activated and release the mystery factor which
inhibits viral replication.  The problem is getting class I loaded.  In
other viral diseases you simply attenuate the virus and inject it.  The
person may get slightly ill but recovers quickly and has a good CD8
immune response against the virus.  You can see the problem with HIV. 
Trial using HIV with whole gene segments knocked out such as nef sound
great but may still not be approved by FDA.  The monkey studies which
used nef deletions caused disease in one animal.  It seems to have
commandeered viral machinery from a different virus and therefore became
replication competant.  It may be useful but more expensive to take out
class I APCs activated so that all the proper costimulatory molecules are
present, load there class I exogenously with a pool of peptides and
inject back into the patient.  

Anyway,  the key is to activate CD8 cells safely.  

PS.  All this media hype on IL2 is just that.  In fact high dose IL2 will
activate CD4 cells non-specifically and make them more susceptable to HIV
infection.  It has been proposed that IL2 pulsing may be more effective
not in boosting CD4 cells but CD8 cell proliferation/activation. 
Remember recent nature papers have shown that the trunover of CD4 is
already virtually maximal and possibly even exhaustive.



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