title: Mosaic vaccines elicit CD8+ T lymphocyte responses that confer enhanced immune coverage of diverse HIV strains in monkeys.
abstract: An effective HIV vaccine must elicit immune responses that recognize genetically diverse viruses. It must generate CD8+ T lymphocytes that control HIV replication and CD4+ T lymphocytes that provide help for the generation and maintenance of both cellular and humoral immune responses against the virus. Creating immunogens that can elicit cellular immune responses against the genetically varied circulating isolates of HIV presents a key challenge for creating an HIV vaccine. Polyvalent mosaic immunogens derived by in silico recombination of natural strains of HIV are designed to induce cellular immune responses that recognize genetically diverse circulating virus isolates. Here we immunized rhesus monkeys by plasmid DNA prime and recombinant vaccinia virus boost with vaccine constructs expressing either consensus or polyvalent mosaic proteins. As compared to consensus immunogens, the mosaic immunogens elicited CD8+ T lymphocyte responses to more epitopes of each viral protein than did the consensus immunogens and to more variant sequences of CD8+ T lymphocyte epitopes. This increased breadth and depth of epitope recognition may contribute both to protection against infection by genetically diverse viruses and to the control of variant viruses that emerge as they mutate away from recognition by cytotoxic T lymphocytes.
authors.affiliation: Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Sampa
authors.initials: S
authors.lastname: Santra
authors.forename: Hua-Xin
authors.initials: HX
authors.lastname: Liao
authors.forename: Ruijin
authors.initials: R
authors.lastname: Zhang
authors.forename: Mark
authors.initials: M
authors.lastname: Muldoon
authors.forename: Sydeaka
authors.initials: S
authors.lastname: Watson
authors.forename: Will
authors.initials: W
authors.lastname: Fischer
authors.forename: James
authors.initials: J
authors.lastname: Theiler
authors.forename: James
authors.initials: J
authors.lastname: Szinger
authors.forename: Harikrishnan
authors.initials: H
authors.lastname: Balachandran
authors.forename: Adam
authors.initials: A
authors.lastname: Buzby
authors.forename: David
authors.initials: D
authors.lastname: Quinn
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Parks
authors.forename: Chun-Yen
authors.initials: CY
authors.lastname: Tsao
authors.forename: Angela
authors.initials: A
authors.lastname: Carville
authors.forename: Keith G
authors.initials: KG
authors.lastname: Mansfield
authors.forename: George N
authors.initials: GN
authors.lastname: Pavlakis
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Felber
authors.forename: Barton F
authors.initials: BF
authors.lastname: Haynes
authors.forename: Bette T
authors.initials: BT
authors.lastname: Korber
authors.forename: Norman L
authors.initials: NL
authors.lastname: Letvin
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006678:HIV / Q000276:immunology*; D015488:HIV Antigens / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D007111:Immunity, Cellular / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D018655:Lymphocyte Count; D008253:Macaca mulatta / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D018984:Epitopes, T-Lymphocyte; D015488:HIV Antigens; D014614:Vaccines, Synthetic; D054301:gag Gene Products, Human Immunodeficiency Virus; D054311:nef Gene Products, Human Immunodeficiency Virus