Heterologous envelope immunogens contribute to AIDS vaccine protection in rhesus monkeys.
Because a strategy to elicit broadly neutralizing anti-human immunodeficiency virus type 1 (HIV-1) antibodies has not yet been found, the role of an Env immunogen in HIV-1 vaccine candidates remains undefined. We sought to determine whether an HIV-1 Env immunogen genetically disparate from the Env of the challenge virus can contribute to protective immunity. We vaccinated Indian-origin rhesus monkeys with Gag-Pol-Nef immunogens, alone or in combination with Env immunogens that were either matched or mismatched with the challenge virus. These animals were then challenged with a pathogenic simian-human immunodeficiency virus. The vaccine regimen included a plasmid DNA prime and replication-defective adenoviral vector boost. Vaccine regimens that included the matched or mismatched Env immunogens conferred better protection against CD4(+) T-lymphocyte loss than that seen with comparable regimens that did not include Env immunogens. This increment in protective immunity was associated with anamnestic Env-specific cellular immunity that developed in the early days following viral challenge. These data suggest that T-lymphocyte immunity to Env can broaden the protective cellular immune response to HIV despite significant sequence diversity of the strains of the Env immunogens and can contribute to immune protection in this AIDS vaccine model.
Letvin
Norman L
NL
Vaccine Research Center, National Institutes of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland 20892-3005, USA. nletvin@bidmc.harvard.edu
Huang
Yue
Y
Chakrabarti
Bimal K
BK
Xu
Ling
L
Seaman
Michael S
MS
Beaudry
Kristin
K
Korioth-Schmitz
Birgit
B
Yu
Faye
F
Rohne
Daniela
D
Martin
Kristi L
KL
Miura
Ayako
A
Kong
Wing-Pui
WP
Yang
Zhi-Yong
ZY
Gelman
Rebecca S
RS
Golubeva
Olga G
OG
Montefiori
David C
DC
Mascola
John R
JR
Nabel
Gary J
GJ
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000256:Adenoviridae / Q000235:genetics / Q000276:immunology; D000818:Animals; D018791:CD4 Lymphocyte Count; D015685:Fusion Proteins, gag-pol / Q000235:genetics / Q000276:immunology; D015686:Gene Products, env / Q000235:genetics / Q000276:immunology*; D015693:Gene Products, nef / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D008253:Macaca mulatta; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000276:immunology*; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology; D054311:nef Gene Products, Human Immunodeficiency Virus
D016915:AIDS Vaccines; D015685:Fusion Proteins, gag-pol; D015686:Gene Products, env; D015693:Gene Products, nef; D012367:RNA, Viral; D011994:Recombinant Proteins; D018449:SAIDS Vaccines; D019444:Vaccines, DNA; D054311:nef Gene Products, Human Immunodeficiency Virus