Polyvalent vaccines for optimal coverage of potential T-cell epitopes in global HIV-1 variants.

Published

Journal Article

HIV-1/AIDS vaccines must address the extreme diversity of HIV-1. We have designed new polyvalent vaccine antigens comprised of sets of 'mosaic' proteins, assembled from fragments of natural sequences via a computational optimization method. Mosaic proteins resemble natural proteins, and a mosaic set maximizes the coverage of potential T-cell epitopes (peptides of nine amino acids) for a viral population. We found that coverage of viral diversity using mosaics was greatly increased compared to coverage by natural-sequence vaccine candidates, for both variable and conserved proteins; for conserved HIV-1 proteins, global coverage may be feasible. For example, four mosaic proteins perfectly matched 74% of 9-amino-acid potential epitopes in global Gag sequences; 87% of potential epitopes matched at least 8 of 9 positions. In contrast, a single natural Gag protein covered only 37% (9 of 9) and 67% (8 of 9). Mosaics provide diversity coverage comparable to that afforded by thousands of separate peptides, but, because the fragments of natural proteins are compressed into a small number of native-like proteins, they are tractable for vaccines.

Full Text

Duke Authors

Cited Authors

  • Fischer, W; Perkins, S; Theiler, J; Bhattacharya, T; Yusim, K; Funkhouser, R; Kuiken, C; Haynes, B; Letvin, NL; Walker, BD; Hahn, BH; Korber, BT

Published Date

  • January 1, 2007

Published In

Volume / Issue

  • 13 / 1

Start / End Page

  • 100 - 106

PubMed ID

  • 17187074

Pubmed Central ID

  • 17187074

International Standard Serial Number (ISSN)

  • 1078-8956

Digital Object Identifier (DOI)

  • 10.1038/nm1461

Language

  • eng

Conference Location

  • United States