Background: The efficacy of the CTL component of a future HIV-1 vaccine will depend on the
induction of responses with the most potent antiviral activity and broad HLA class I restriction.
However, current HIV vaccine designs are largely based on viral sequence alignments only, not
incorporating experimental data on T cell function and specificity.
Methods: Here, 950 untreated HIV-1 clade B or -C infected individuals were tested for responses
to sets of 410 overlapping peptides (OLP) spanning the entire HIV-1 proteome. For each OLP, a
“protective ratio” (PR) was calculated as the ratio of median viral loads (VL) between OLP nonresponders
and responders.
Results: For both clades, there was a negative relationship between the PR and the entropy of the
OLP sequence. There was also a significant additive effect of multiple responses to beneficial
OLP. Responses to beneficial OLP were of significantly higher functional avidity than responses
to non-beneficial OLP. They also had superior in-vitro antiviral activities and, importantly, were
at least as predictive of individuals’ viral loads than their HLA class I genotypes.
Conclusions: The data thus identify immunogen sequence candidates for HIV and provide an
approach for T cell immunogen design applicable to other viral infections.
