Technical Report abstract
Nature Medicine 13, 100 - 106 (2006)
Published online: 24 December 2006 | doi:10.1038/nm1461
Polyvalent vaccines for optimal coverage of potential T-cell epitopes in global HIV-1 variants
Will Fischer1,7, Simon Perkins1,7, James Theiler1, Tanmoy Bhattacharya1,2, Karina Yusim1, Robert Funkhouser1, Carla Kuiken1, Barton Haynes3, Norman L Letvin4, Bruce D Walker5, Beatrice H Hahn6 & Bette T Korber1,2
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.
- Los Alamos National Laboratory, Los Alamos, New Mexico 87545, USA.
- Santa Fe Institute, 1399 Hyde Park Road, Santa Fe, New Mexico 87501, USA.
- Duke University, Department of Medicine, Room 107 Circuit Drive, PO Box 3258, Durham, North Carolina 27710, USA.
- Harvard-Beth Israel Deaconess Medical Center, 41 Avenue of Louis Pasteur, Re Room 113, Boston, Massachusetts 02115, USA.
- Harvard Medical School, Massachusetts General Hospital-East, 149 13th Street, Charlestown, Massachusetts 02129, USA.
- University of Alabama at Birmingham, Kaul Building 816 - 720 20th Street South, Birmingham, Alabama 35294, USA.
- These authors contributed equally to this work.
Correspondence to: Bette T Korber1,2 e-mail: btk@lanl.gov
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