Abstract
The development of an effective HIV vaccine is hindered by several obstacles. One of the
leading challenges is the antigenic variability of HIV-1 that is exhibited throughout all
viral gene products but to greatest extent in the viral envelope proteins. This phenomenon
is the result of continuous mutations in the HIV genome and is responsible for the
immune escape of viral mutants. Many studies have suggested that a multivalent vaccine
that elicits broadly cross-reactive antibodies is required to efficiently target antigenic
variability. To this end, we have designed and analyzed a synthetic peptide construct that
mimicked the major variability exhibited in the V3 loops of HIV-1 subtype C isolates.
The peptide construct, described as a multiple epitope immunogen of the V3 loop with 8
branches and termed MEIV3b8, was shown to be non-toxic but highly immunogenic in
experimental animals (mice and rabbits) and produced antibodies that were reactive to V3
loop peptides of various subtypes, variant envelope proteins and whole viral isolates [at
antibody titers 1000 in enzyme-linked immunosorbent assays (ELISAs)]. Furthermore,
functional antibodies were generated in rabbits that mediated neutralization of a
neutralization-sensitive HIV-1 isolate and two distinct primary HIV-1 isolates in several
different neutralization assays (at antibody titres 1213). Additionally, the MEIV3b8
induced both proliferative and inflammatory immune responses in a murine model.Finally, antibodies in the plasma of individuals (n = 148) infected with HIV-1 subtype C,
subtype B and HIV-2 were found to bind to the MEIV3b8 as antigen in ELISAs. Through
these findings, this study demonstrated that the variable MEIV3b8 effectively addressed
antigenic variability and provided evidence that this peptide construct may hold
application in HIV-1 preventative and therapeutic vaccination as well as HIV
immunodiagnosis.
Dr. D. Meyer