HIV Vaccine

George M. Carter gmc0 at ix.netcom.com
Thu Nov 5 11:58:51 EST 1998


"Doug Hosack" <Doug!@nih.gov> wrote:

snip....

>Most approaches today seek to maximize cell-mediated responses rather that
>humoral responses.   There is even speculation that antibody responses to
>HIV are counterproductive.  

That's if one buys the Th1 -> Th2 switch as also meaning an
enhancement of humoral immunity at the expense of CMI.  In mice, this
happens.  In human diseases like schistosomiasis or leprosy, the
prevailing arm of immunity correlates with the severity of
progression.  But I'm not so sure about HIV--while I agree that CMI is
CRITICALLY important, I don't think it is necessarily at the expense
of humoral--and certainly not mucosal immunity as suggested below.

(E.g.,--I'd like people's thoughts on the observation that as AIDS
begins to set in, antibodies to gp120 remain in high titer while p24
abs vanish.)

>It seems that HIV is designed to generate an
>antibody response against useless regions on gp120 in order to protect more
>critical regions.  For this reason, I'm sure that you'll find plenty of
>advise about protocols to generate anti-HIV CTL responses.

>I will suggest a (far-fetched?) protocol to generate an effective IgA
>response to prevent sexually-transmitted HIV infection.  In short, it
>involves the creation of recombinant bacteria that express a protein similar
>to a critical region on gp120.  

Specifically?  An exposed, conserved region?  I like this idea.

>In productive HIV infection, the immune
>system does not generate antibodies to this region, probably because of an
>antibody response to an adjacent "decoy" epitope.  This protocol is designed
>to present the critical epitope without decoy epitope interference.

Or an epitope that merely is able to mutate readily, as does the V3
loop.  (Indeed, one might accelerate progression if the vaccine
generates an antibody response that induces a switch from
non-syncytia to syncytia forming virus.)

>The basis of the approach is based upon the ability of a protein known as
>cyanovirin-N to bind gp120 and prevent infection by all strains of HIV-1,
>HIV-2, SIV and FIV tested thus far.  For background, please read
>http://www.ama-assn.org/special/hiv/newsline/special/jamadb/cvn.htm

It'll be interesting to see how it can be done to raise human
antibodies, of course!  (Using SCID-hu?)

Remaining mouse study info snipped....

		George M. Carter





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