| dc.description.abstract | Background: Current HIV vaccine candidates have been based on
the conventional views of viral infection and attempt to induce
broad T cell responses to HIV-1. Until now, the candidate vaccines
based on such approach either failed to provide protection or produced
modest effect that is not satisfactory for an effective vaccine.
Since these vaccine candidates were not based on the correlates of
protection against HIV-1 infection, improving such understanding
could be critical for successful vaccine development.
Methods: A subset of women enrolled in the Pumwani Sexworker
Cohort remain uninfected by HIV-1 despite repeated
exposures through sex work. This resistance to HIV-1 infection is
associated with several alleles of Human Leukocyte Antigens
(HLAs) and specific CD8+ and CD4+ T cell responses. In this
study we systematically analyzed HIV-1 clade A and D Gag
epitope profiles of two HLA class I alleles associated with different
outcomes of HIV-1 infection, A*0101 is significantly associated
with slower seroconversion while B*0702 is associated with
rapid seroconversion. We screened a Gag peptide library with
iTopia Epitope Discovery System to compare the peptide binding
capacity of these two alleles. The identified peptides were characterized
by affinity and off-rate assays and confirmed by interferon
gamma ELISPOT assays using patient peripheral blood
mononuclear cells.
Results: A*0101, an allele associated with protection from HIV-1
infection, only binds to 3 epitopes in Gag. Whereas, B*0702, an
allele associated with rapid disease progression, has 30 Gag epitopes.
There is no significant difference in peptide binding affinity,
off-rate, ELISPOT SFU values and epitope specific Tem/Tcm
frequencies.
Conclusion: In contrast to the broad peptide binding spectrum of
B*0702, A*0101’s epitopes are narrowly directed. Observations of
this study question the current approach for HIV-1 vaccine development
and propose a different vaccine development strategy. | en |
