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

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 Todd, Norman L. Letvin, Jinghe Huang, Martha C. Nason, James A. Hoxie, Peter D. Kwong, Mark Connors, Srinivas S. Rao, John R. Mascola, Gary J. Nabel

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article number243ra88
JournalScience translational medicine
Volume6
Issue number243
DOIs
StatePublished - Jul 2 2014

ASJC Scopus subject areas

  • Medicine(all)

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    Pegu, A., Yang, Z. Y., Boyington, J. C., Wu, L., Ko, S. Y., Schmidt, S. D., McKee, K., Kong, W. P., Shi, W., Chen, X., Todd, J. P., Letvin, N. L., Huang, J., Nason, M. C., Hoxie, J. A., Kwong, P. D., Connors, M., Rao, S. S., Mascola, J. R., & Nabel, G. J. (2014). Neutralizing antibodies to HIV-1 envelope protect more effectively in vivo than those to the CD4 receptor. Science translational medicine, 6(243), [243ra88]. https://doi.org/10.1126/scitranslmed.3008992