Mosaic vaccines elicit CD8+ T lymphocyte responses that confer enhanced immune coverage of diverse HIV strains in monkeys.
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.
Santra
Sampa
S
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
Liao
Hua-Xin
HX
Zhang
Ruijin
R
Muldoon
Mark
M
Watson
Sydeaka
S
Fischer
Will
W
Theiler
James
J
Szinger
James
J
Balachandran
Harikrishnan
H
Buzby
Adam
A
Quinn
David
D
Parks
Robert J
RJ
Tsao
Chun-Yen
CY
Carville
Angela
A
Mansfield
Keith G
KG
Pavlakis
George N
GN
Felber
Barbara K
BK
Haynes
Barton F
BF
Korber
Bette T
BT
Letvin
Norman L
NL
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
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