title: HIV-1 DNA/MVA vaccination reduces the per exposure probability of infection during repeated mucosal SHIV challenges.
abstract: 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.
authors.affiliation: 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
authors.forename: Dennis
authors.initials: D
authors.lastname: Ellenberger
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Otten
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.forename: Michael
authors.initials: M
authors.lastname: Aidoo
authors.forename: I Vanessa
authors.initials: IV
authors.lastname: Rodriguez
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Sariol
authors.forename: Melween
authors.initials: M
authors.lastname: Martinez
authors.forename: Michael
authors.initials: M
authors.lastname: Monsour
authors.forename: Linda
authors.initials: L
authors.lastname: Wyatt
authors.forename: Michael G
authors.initials: MG
authors.lastname: Hudgens
authors.forename: Edmundo
authors.initials: E
authors.lastname: Kraiselburd
authors.forename: Bernard
authors.initials: B
authors.lastname: Moss
authors.forename: Harriet
authors.initials: H
authors.lastname: Robinson
authors.forename: Thomas
authors.initials: T
authors.lastname: Folks
authors.forename: Salvatore
authors.initials: S
authors.lastname: Butera
mesh_terms: 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*
chemical_list: D016915:AIDS Vaccines; D019444:Vaccines, DNA