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

被引:465
作者
Hessell, Ann J. [1 ,2 ]
Poignard, Pascal [1 ,2 ]
Hunter, Meredith [3 ]
Hangartner, Lars [4 ]
Tehrani, David M. [1 ,2 ]
Bleeker, Wim K. [5 ]
Parren, Paul W. H. I. [5 ]
Marx, Preston A. [3 ]
Burton, Dennis R. [1 ,2 ]
机构
[1] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA
[2] Scripps Res Inst, Int AIDS Vaccine Initiat Neutralizing Antibody Ct, La Jolla, CA 92037 USA
[3] Tulane Univ, Tulane Natl Primate Res Ctr, Covington, LA USA
[4] Univ Zurich, Inst Med Virol, Zurich, Switzerland
[5] Genmab, Utrecht, Netherlands
基金
美国国家卫生研究院;
关键词
HUMAN-IMMUNODEFICIENCY-VIRUS; HIV PRECLINICAL INTERVENTIONS; HIV-1/SIV CHIMERIC VIRUS; NEUTRALIZING ANTIBODY; SEXUAL TRANSMISSION; PASSIVE TRANSFER; EXPOSURES; INFECTION; EFFICIENT; STRATEGY;
D O I
10.1038/nm.1974
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Neutralizing antibodies are thought to be crucial for HIV vaccine protection, but studies in animal models suggest that high antibody concentrations are required(1). 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(2-4). 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.
引用
收藏
页码:951 / U155
页数:5
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