Journal Article

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

Yusim, Karina, Korber, Bette T, Funkhouser, Robert, Haynes, Barton, Perkins, Simon, Fischer, Will, Bhattacharya, Tanmoy, Walker, Bruce D, Hahn, Beatrice H, Theiler, James, Letvin, Norman L, Kuiken, Carla

2007

Overview

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.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: Acquired immune deficiency syndrome / AIDS / AIDS Vaccines - genetics / AIDS Vaccines - immunology / Algorithms / Amino acids / Biomedical and Life Sciences / Biomedicine / Cancer Research / Epitopes, T-Lymphocyte - immunology / Gene Products, env - genetics / Gene Products, env - immunology / Gene Products, gag - genetics / Gene Products, gag - immunology / Gene Products, nef - genetics / Gene Products, nef - immunology / Gene Products, rev - genetics / Gene Products, rev - immunology / Gene Products, tat - genetics / Gene Products, tat - immunology / Gene Products, vif - genetics / Gene Products, vif - immunology / Genetic Heterogeneity / Genetic Variation / HIV / HIV Antigens - genetics / HIV Antigens - immunology / HIV Infections - immunology / HIV Infections - prevention & control / HIV Infections - virology / HIV-1 - genetics / HIV-1 - immunology / Human immunodeficiency virus / Human immunodeficiency virus 1 / Humans / Infectious Diseases / Metabolic Diseases / Molecular Medicine / nef Gene Products, Human Immunodeficiency Virus / Neurosciences / Peptides / Proteins / rev Gene Products, Human Immunodeficiency Virus / tat Gene Products, Human Immunodeficiency Virus / technical-report / Vaccines / vif Gene Products, Human Immunodeficiency Virus / Virology