HIV-1 DNA/MVA vaccination reduces the per exposure probability of infection during repeated mucosal SHIV challenges

Dennis Ellenberger, Ronald A. Otten, Bin Li, Michael Aidoo, I. Vanessa Rodriguez, Carlos A. Sariol, Melween Martinez, Michael Monsour, Linda Wyatt, Michael G. Hudgens, Edmundo Kraiselburd, Bernard Moss, Harriet Robinson, Thomas Folks, Salvatore Butera

    Research output: Contribution to journalArticle

    41 Scopus citations

    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.

    Original languageEnglish (US)
    Pages (from-to)216-225
    Number of pages10
    JournalVirology
    Volume352
    Issue number1
    DOIs
    StatePublished - Aug 15 2006

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    Keywords

    • DNA/MVA
    • Human sexual transmission
    • Mucosal challenge
    • Non-human primate model
    • Repetitive virus challenge
    • SHIV
    • Vaccine

    ASJC Scopus subject areas

    • Virology

    Cite this

    Ellenberger, D., Otten, R. A., Li, B., Aidoo, M., Rodriguez, I. V., Sariol, C. A., Martinez, M., Monsour, M., Wyatt, L., Hudgens, M. G., Kraiselburd, E., Moss, B., Robinson, H., Folks, T., & Butera, S. (2006). HIV-1 DNA/MVA vaccination reduces the per exposure probability of infection during repeated mucosal SHIV challenges. Virology, 352(1), 216-225. https://doi.org/10.1016/j.virol.2006.04.005