Short communication: HIV-1 Nef protein carries multiple epitopes suitable for induction of cellular immunity for an HIV vaccine in Africa

Abstract

Using the early protein HIV Nef, new HLA class I binding epitopes of importance for immune responses to HIV were predicted for common African alleles. In total we identified 45 epitopes previously not described for the HLA alleles A*30:01, A*30:02, B*58:01, and C*07:01 and compared them to reported epitopes, primarily from HLA-A*02:01, from the Los Alamos database and our own vaccine studies. Related to its small size, the Nef gene/protein appears to be able to contribute effectively to confer both stronger and broader cellular immunogenicity to an HIV-1 vaccine. We also propose feasible mutations of such an additional vaccine antigen to preserve its immunogenicity, modified not to confer HLA or CD4(+) down-regulating activities. This article includes data on a valuable HIV immunogenic component for a vaccine in Africa.

FIG. 1.

The top 30 Nef epitopes each of HIV-1 subtypes B (A) and C (B) according to proteasomal cleavage, TAP transport, and MHC binding combined predictions. Peptides marked as black represent the highest scoring epitopes, with scores over 1. Gray peptides represent medium scoring epitopes in the range of −1 and 1, and low scoring epitopes under −1 are colored in white. The cutoffs were selected to clearly distinguish the top scoring peptides from the medium and lower scoring ones.

FIG. 2.

(A) Previously published epitopes for HIV-1 Nef (black) and the 10 best predicted epitopes (hollow) by allele denoted on HXB2 aa positions. Regions with the highest frequency of epitopes are marked by lines for known (black) and predicted novel (hollow) epitopes. Arrows indicate feasible mutations: for myristylation at aa G2, association with polyproline at aa VGFP65-69, and/or dimerization at aa R105, R106, and D123. (B) The Nef protein variation across all subtypes, including variants with additional C-terminal sequences.