title: Polyvalent vaccines for optimal coverage of potential T-cell epitopes in global HIV-1 variants.
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.
authors.affiliation: Los Alamos National Laboratory, Los Alamos, New Mexico 87545, USA.
authors.forename: Will
authors.initials: W
authors.lastname: Fischer
authors.forename: Simon
authors.initials: S
authors.lastname: Perkins
authors.forename: James
authors.initials: J
authors.lastname: Theiler
authors.forename: Tanmoy
authors.initials: T
authors.lastname: Bhattacharya
authors.forename: Karina
authors.initials: K
authors.lastname: Yusim
authors.forename: Robert
authors.initials: R
authors.lastname: Funkhouser
authors.forename: Carla
authors.initials: C
authors.lastname: Kuiken
authors.forename: Barton
authors.initials: B
authors.lastname: Haynes
authors.forename: Norman L
authors.initials: NL
authors.lastname: Letvin
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
authors.forename: Beatrice H
authors.initials: BH
authors.lastname: Hahn
authors.forename: Bette T
authors.initials: BT
authors.lastname: Korber
mesh_terms: D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology*; D000465:Algorithms; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015686:Gene Products, env / Q000235:genetics / Q000276:immunology; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology; D015693:Gene Products, nef / Q000235:genetics / Q000276:immunology; D015694:Gene Products, rev / Q000235:genetics / Q000276:immunology; D015696:Gene Products, tat / Q000235:genetics / Q000276:immunology; D016346:Gene Products, vif / Q000235:genetics / Q000276:immunology; D018740:Genetic Heterogeneity; D014644:Genetic Variation; D015488:HIV Antigens / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D054311:nef Gene Products, Human Immunodeficiency Virus; D054321:rev Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus; D054320:vif Gene Products, Human Immunodeficiency Virus
chemical_list: D016915:AIDS Vaccines; D018984:Epitopes, T-Lymphocyte; D015686:Gene Products, env; D015683:Gene Products, gag; D015693:Gene Products, nef; D015694:Gene Products, rev; D015696:Gene Products, tat; D016346:Gene Products, vif; D015488:HIV Antigens; D054311:nef Gene Products, Human Immunodeficiency Virus; D054321:rev Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus; D054320:vif Gene Products, Human Immunodeficiency Virus