Polyvalent vaccines for optimal coverage of potential T-cell epitopes in global HIV-1 variants (original) (raw)

Nature Medicine volume 13, pages 100–106 (2007)Cite this article

Abstract

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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Article Open access 09 January 2024

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Acknowledgements

The authors thank J.H. Fischer for helpful comments on the manuscript. This work was funded through an internal directed-research grant for vaccine design at Los Alamos National Laboratory (to W.F., S.P., T.B., J.T., B.T.K., K.Y., R.F. and B.H.H.), a US National Institutes of Health (NIH) HIVRAD grant (P01 consortium (to B.H., B.H.H. and N.L.).

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Author notes

  1. Will Fischer and Simon Perkins: These authors contributed equally to this work.

Authors and Affiliations

  1. Los Alamos National Laboratory, Los Alamos, 87545, New Mexico, USA
    Will Fischer, Simon Perkins, James Theiler, Tanmoy Bhattacharya, Karina Yusim, Robert Funkhouser, Carla Kuiken & Bette T Korber
  2. Santa Fe Institute, 1399 Hyde Park Road, Santa Fe, 87501, New Mexico, USA
    Tanmoy Bhattacharya & Bette T Korber
  3. Department of Medicine, Duke University, Room 107 Circuit Drive, PO Box 3258, Durham, 27710, North Carolina, USA
    Barton Haynes
  4. Harvard-Beth Israel Deaconess Medical Center, 41 Avenue of Louis Pasteur, Re Room 113, Boston, 02115, Massachusetts, USA
    Norman L Letvin
  5. Harvard Medical School, Massachusetts General Hospital-East, 149 13th Street, Charlestown, 02129, Massachusetts, USA
    Bruce D Walker
  6. University of Alabama at Birmingham, Kaul Building 816 - 720 20th Street South, Birmingham, 35294, Alabama, USA
    Beatrice H Hahn

Authors

  1. Will Fischer
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  2. Simon Perkins
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  3. James Theiler
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  4. Tanmoy Bhattacharya
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  5. Karina Yusim
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  6. Robert Funkhouser
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  7. Carla Kuiken
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  8. Barton Haynes
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  9. Norman L Letvin
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  10. Bruce D Walker
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  11. Beatrice H Hahn
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  12. Bette T Korber
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Corresponding author

Correspondence toBette T Korber.

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A patent application has been made, covering the methods and materials presented in this paper.

Supplementary information

Supplementary Fig. 1

Full overall coverage of vaccine candidates: coverage of nine-mers in B-clade, C-clade, and M-group sequences using different input data sets for mosaic optimization, allowing different numbers of antigens, and comparing to different candidate vaccines. (PDF 2773 kb)

Supplementary Fig. 2

The distribution of nine-mers by frequency of occurrence in natural, consensus, and mosaic sequences. (PDF 546 kb)

Supplementary Fig. 3

HLA binding potential of vaccine candidates. (PDF 736 kb)

Supplementary Data (PDF 212 kb)

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Fischer, W., Perkins, S., Theiler, J. et al. Polyvalent vaccines for optimal coverage of potential T-cell epitopes in global HIV-1 variants.Nat Med 13, 100–106 (2007). https://doi.org/10.1038/nm1461

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