Letter abstract
Nature Medicine 15, 951 - 954 (2009)
Published online: 7 June 2009 | doi:10.1038/nm.1974
Effective, low-titer antibody protection against low-dose repeated mucosal SHIV challenge in macaques
Ann J Hessell1, Pascal Poignard1, Meredith Hunter2, Lars Hangartner3, David M Tehrani1, Wim K Bleeker4, Paul W H I Parren4, Preston A Marx2 & Dennis R Burton1
Neutralizing antibodies are thought to be crucial for HIV vaccine protection, but studies in animal models suggest that high antibody concentrations are required1. 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 virus2, 3, 4. 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.
- Department of Immunology and Microbial Science and International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, California, USA.
- Tulane National Primate Research Center, Tulane University, Covington, Louisiana, USA.
- University of Zurich, Institute of Medical Virology, Zürich, Switzerland.
- Genmab, Utrecht, The Netherlands.
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