Effective, low-titer antibody protection against low-dose repeated mucosal SHIV challenge in macaques

Ann J. Hessell, Pascal Poignard, Meredith Hunter, Lars Hangartner, David M. Tehrani, Wim K. Bleeker, Paul W.H.I. Parren, Preston A. Marx, Dennis R. Burton

Research output: Contribution to journalArticlepeer-review

425 Scopus citations

Abstract

Neutralizing antibodies are thought to be crucial for HIV vaccine protection, but studies in animal models suggest that high antibody concentrations are required. This is a major potential hurdle for vaccine design. However, these studies typically apply a large virus inoculum to ensure infection in control animals in single-challenge experiments. In contrast, most human infection via sexual encounter probably involves repeated exposures to much lower doses of virus. Therefore, animal studies may have provided an overestimate of the levels of antibodies required for protection in humans. We investigated whether plasma concentrations of antibody corresponding to relatively modest neutralization titers in vitro could protect macaques from repeated intravaginal exposure to low doses of a simian immunodeficiency virus-HIV chimera (SHIV) that uses the CC chemokine receptor 5 (CCR5) co-receptor. An effector function-deficient variant of the neutralizing antibody was also included. The results show that a substantially larger number of challenges is required to infect macaques treated with neutralizing antibody than control antibody-treated macaques, and support the notion that effector function may contribute to antibody protection. Overall, the results imply that lower amounts of antibody than previously considered protective may provide benefit in the context of typical human exposure to HIV-1.

Original languageEnglish (US)
Pages (from-to)951-954
Number of pages4
JournalNature medicine
Volume15
Issue number8
DOIs
StatePublished - Aug 2009
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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