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

Publication ,  Journal Article
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 in: Nat Med
January 2007

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.

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Published In

Nat Med

DOI

ISSN

1078-8956

Publication Date

January 2007

Volume

13

Issue

1

Start / End Page

100 / 106

Location

United States

Related Subject Headings

  • vif Gene Products, Human Immunodeficiency Virus
  • tat Gene Products, Human Immunodeficiency Virus
  • rev Gene Products, Human Immunodeficiency Virus
  • nef Gene Products, Human Immunodeficiency Virus
  • Immunology
  • Humans
  • HIV-1
  • HIV Infections
  • HIV Antigens
  • Genetic Variation
 

Citation

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Fischer, W., Perkins, S., Theiler, J., Bhattacharya, T., Yusim, K., Funkhouser, R., … Korber, B. T. (2007). Polyvalent vaccines for optimal coverage of potential T-cell epitopes in global HIV-1 variants. Nat Med, 13(1), 100–106. https://doi.org/10.1038/nm1461
Fischer, Will, Simon Perkins, James Theiler, Tanmoy Bhattacharya, Karina Yusim, Robert Funkhouser, Carla Kuiken, et al. “Polyvalent vaccines for optimal coverage of potential T-cell epitopes in global HIV-1 variants.Nat Med 13, no. 1 (January 2007): 100–106. https://doi.org/10.1038/nm1461.
Fischer W, Perkins S, Theiler J, Bhattacharya T, Yusim K, Funkhouser R, et al. Polyvalent vaccines for optimal coverage of potential T-cell epitopes in global HIV-1 variants. Nat Med. 2007 Jan;13(1):100–6.
Fischer, Will, et al. “Polyvalent vaccines for optimal coverage of potential T-cell epitopes in global HIV-1 variants.Nat Med, vol. 13, no. 1, Jan. 2007, pp. 100–06. Pubmed, doi:10.1038/nm1461.
Fischer W, Perkins S, Theiler J, Bhattacharya T, Yusim K, Funkhouser R, Kuiken C, Haynes B, Letvin NL, Walker BD, Hahn BH, Korber BT. Polyvalent vaccines for optimal coverage of potential T-cell epitopes in global HIV-1 variants. Nat Med. 2007 Jan;13(1):100–106.

Published In

Nat Med

DOI

ISSN

1078-8956

Publication Date

January 2007

Volume

13

Issue

1

Start / End Page

100 / 106

Location

United States

Related Subject Headings

  • vif Gene Products, Human Immunodeficiency Virus
  • tat Gene Products, Human Immunodeficiency Virus
  • rev Gene Products, Human Immunodeficiency Virus
  • nef Gene Products, Human Immunodeficiency Virus
  • Immunology
  • Humans
  • HIV-1
  • HIV Infections
  • HIV Antigens
  • Genetic Variation