Neutralizing antibodies to HIV-1 envelope protect more effectively in vivo than those to the CD4 receptor

作者：Amarendra Pegu, Zhi-Yong Yang, Jeffrey C. Boyington, Lan Wu, Sung‐Youl Ko, Stephen D. Schmidt, Krisha McKee, Wing‐Pui Kong, Wei Shi, Xuejun Chen, John-Paul M. Todd, Norman L. Letvin, Jinghe Huang, Martha Nason, James A. Hoxie, Peter D. Kwong, Mark Connors, Srinivas S. Rao, John R. Mascola, Gary J. Nabel · 发表于：Science Translational Medicine · 年份：2014 · DOI：10.1126/scitranslmed.3008992 · 被引用次数：247 · 研究领域：HIV Research and Treatment、Immune Cell Function and Interaction、T-cell and B-cell Immunology

HIV-1 infection depends on effective viral entry mediated by the interaction of its envelope (Env) glycoprotein with specific cell surface receptors. Protective antiviral antibodies generated by passive or active immunization must prevent these interactions. Because the HIV-1 Env is highly variable, attention has also focused on blocking the HIV-1 primary cell receptor CD4. We therefore analyzed the in vivo protective efficacy of three potent neutralizing monoclonal antibodies (mAbs) to HIV-1 Env compared to an antibody against the CD4 receptor. Protection was assessed after mucosal challenge of rhesus macaques with simian/HIV (SHIV). Despite its comparable or greater neutralization potency in vitro, the anti-CD4 antibody did not provide effective protection in vivo, whereas the HIV-1-specific mAbs VRC01, 10E8, and PG9, targeting the CD4 binding site, membrane-proximal, and V1V2 glycan Env regions, respectively, conferred complete protection, albeit at different relative potencies. These findings demonstrate the protective efficacy of broadly neutralizing antibodies directed to the HIV-1 Env and suggest that targeting the HIV-1 Env is preferable to the cell surface receptor CD4 for the prevention of HIV-1 transmission.