Mosaic HIV-1 vaccines expand the breadth and depth of cellular immune responses in rhesus monkeys.
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.
Barouch
Dan H
DH
Division of Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA. dbarouch@bidmc.harvard.edu
O'Brien
Kara L
KL
Simmons
Nathaniel L
NL
King
Sharon L
SL
Abbink
Peter
P
Maxfield
Lori F
LF
Sun
Ying-Hua
YH
La Porte
Annalena
A
Riggs
Ambryice M
AM
Lynch
Diana M
DM
Clark
Sarah L
SL
Backus
Katherine
K
Perry
James R
JR
Seaman
Michael S
MS
Carville
Angela
A
Mansfield
Keith G
KG
Szinger
James J
JJ
Fischer
Will
W
Muldoon
Mark
M
Korber
Bette
B
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
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