title: Mosaic HIV-1 vaccines expand the breadth and depth of cellular immune responses in rhesus monkeys.
abstract: The worldwide diversity of HIV-1 presents an unprecedented challenge for vaccine development. Antigens derived from natural HIV-1 sequences have elicited only a limited breadth of cellular immune responses in nonhuman primate studies and clinical trials to date. Polyvalent 'mosaic' antigens, in contrast, are designed to optimize cellular immunologic coverage of global HIV-1 sequence diversity. Here we show that mosaic HIV-1 Gag, Pol and Env antigens expressed by recombinant, replication-incompetent adenovirus serotype 26 vectors markedly augmented both the breadth and depth without compromising the magnitude of antigen-specific T lymphocyte responses as compared with consensus or natural sequence HIV-1 antigens in rhesus monkeys. Polyvalent mosaic antigens therefore represent a promising strategy to expand cellular immunologic vaccine coverage for genetically diverse pathogens such as HIV-1.
authors.affiliation: Division of Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA. dbarouch@bidmc.harvard.edu
authors.forename: Dan H
authors.initials: DH
authors.lastname: Barouch
authors.forename: Kara L
authors.initials: KL
authors.lastname: O'Brien
authors.forename: Nathaniel L
authors.initials: NL
authors.lastname: Simmons
authors.forename: Sharon L
authors.initials: SL
authors.lastname: King
authors.forename: Peter
authors.initials: P
authors.lastname: Abbink
authors.forename: Lori F
authors.initials: LF
authors.lastname: Maxfield
authors.forename: Ying-Hua
authors.initials: YH
authors.lastname: Sun
authors.forename: Annalena
authors.initials: A
authors.lastname: La Porte
authors.forename: Ambryice M
authors.initials: AM
authors.lastname: Riggs
authors.forename: Diana M
authors.initials: DM
authors.lastname: Lynch
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Clark
authors.forename: Katherine
authors.initials: K
authors.lastname: Backus
authors.forename: James R
authors.initials: JR
authors.lastname: Perry
authors.forename: Michael S
authors.initials: MS
authors.lastname: Seaman
authors.forename: Angela
authors.initials: A
authors.lastname: Carville
authors.forename: Keith G
authors.initials: KG
authors.lastname: Mansfield
authors.forename: James J
authors.initials: JJ
authors.lastname: Szinger
authors.forename: Will
authors.initials: W
authors.lastname: Fischer
authors.forename: Mark
authors.initials: M
authors.lastname: Muldoon
authors.forename: Bette
authors.initials: B
authors.lastname: Korber
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology* / Q000494:pharmacology*; D000818:Animals; D000917:Antibody Formation / Q000276:immunology / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000502:physiology; D015488:HIV Antigens / Q000276:immunology; D016333:HIV Protease / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D007111:Immunity, Cellular / Q000276:immunology / Q000502:physiology; D008213:Lymphocyte Activation / Q000276:immunology / Q000502:physiology; D008253:Macaca mulatta / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology; D014614:Vaccines, Synthetic; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D018984:Epitopes, T-Lymphocyte; D015488:HIV Antigens; D010446:Peptide Fragments; D014614:Vaccines, Synthetic; D054299:env Gene Products, Human Immunodeficiency Virus; D054301:gag Gene Products, Human Immunodeficiency Virus; D016333:HIV Protease