HIV-1 DNA/MVA vaccination reduces the per exposure probability of infection during repeated mucosal SHIV challenges.
Historically, HIV vaccines specifically designed to raise cellular immunity resulted in protection from disease progression but not infection when tested in monkeys challenged with a single high virus exposure. An alternative approach, more analogous to human sexual exposures, is to repetitively challenge immunized monkeys with a much lower dose of virus until systemic infection is documented. Using these conditions to mimic human sexual transmission, we found that a multi-protein DNA/MVA HIV-1 vaccine is indeed capable of protecting rhesus monkeys against systemic infection when repeatedly challenged with a highly heterologous immunodeficiency virus (SHIV). Furthermore, this repetitive challenge approach allowed us to calculate per-exposure probability of infection, an observed vaccine efficacy of 64%, and undertake a systematic analysis for correlates of protection based on exposures needed to achieve infection. Therefore, improved non-human primate models for vaccine efficacy can provide novel insight and perhaps renew expectations for positive outcomes of human HIV clinical trials.
Ellenberger
Dennis
D
Laboratory Branch, Division of HIV/AIDS Prevention, National Center for HIV, STD and TB Prevention, Centers for Disease Control and Prevention, Mail Stop G-19, 1600 Clifton Road, Atlanta, GA 30333, USA. dellenberger@cdc.gov
Otten
Ronald A
RA
Li
Bin
B
Aidoo
Michael
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Rodriguez
I Vanessa
IV
Sariol
Carlos A
CA
Martinez
Melween
M
Monsour
Michael
M
Wyatt
Linda
L
Hudgens
Michael G
MG
Kraiselburd
Edmundo
E
Moss
Bernard
B
Robinson
Harriet
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Folks
Thomas
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Butera
Salvatore
S
D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D000285:Administration, Rectal; D000818:Animals; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D006801:Humans; D008253:Macaca mulatta; D009092:Mucous Membrane / Q000821:virology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000472:pathogenicity*; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology*
D016915:AIDS Vaccines; D019444:Vaccines, DNA