title: Neutralizing antibodies to HIV-1 envelope protect more effectively in vivo than those to the CD4 receptor.
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.
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), 40 Convent Drive, Bethesda, MD 20892, USA.
authors.forename: Amarendra
authors.initials: A
authors.lastname: Pegu
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), 40 Convent Drive, Bethesda, MD 20892, USA.
authors.forename: Zhi-yong
authors.initials: ZY
authors.lastname: Yang
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), 40 Convent Drive, Bethesda, MD 20892, USA.
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Boyington
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), 40 Convent Drive, Bethesda, MD 20892, USA.
authors.forename: Lan
authors.initials: L
authors.lastname: Wu
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), 40 Convent Drive, Bethesda, MD 20892, USA.
authors.forename: Sung-Youl
authors.initials: SY
authors.lastname: Ko
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), 40 Convent Drive, Bethesda, MD 20892, USA.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Schmidt
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), 40 Convent Drive, Bethesda, MD 20892, USA.
authors.forename: Krisha
authors.initials: K
authors.lastname: McKee
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), 40 Convent Drive, Bethesda, MD 20892, USA.
authors.forename: Wing-Pui
authors.initials: WP
authors.lastname: Kong
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), 40 Convent Drive, Bethesda, MD 20892, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), 40 Convent Drive, Bethesda, MD 20892, USA.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Chen
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), 40 Convent Drive, Bethesda, MD 20892, USA.
authors.forename: John-Paul
authors.initials: JP
authors.lastname: Todd
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), 40 Convent Drive, Bethesda, MD 20892, USA. Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, RE113, P. O. Box 15732, Boston, MA 02115, USA.
authors.forename: Norman L
authors.initials: NL
authors.lastname: Letvin
authors.affiliation: HIV-Specific Immunity Section, Laboratory of Immunoregulation, NIAID, NIH, Bethesda, MD 20892, USA.
authors.forename: Jinghe
authors.initials: J
authors.lastname: Huang
authors.affiliation: Biostatistics Research Branch, NIAID, NIH, Bethesda, MD 20892, USA.
authors.forename: Martha C
authors.initials: MC
authors.lastname: Nason
authors.affiliation: Biostatistics Research Branch, NIAID, NIH, Bethesda, MD 20892, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Hoxie
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), 40 Convent Drive, Bethesda, MD 20892, USA.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Kwong
authors.affiliation: HIV-Specific Immunity Section, Laboratory of Immunoregulation, NIAID, NIH, Bethesda, MD 20892, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Connors
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), 40 Convent Drive, Bethesda, MD 20892, USA.
authors.forename: Srinivas S
authors.initials: SS
authors.lastname: Rao
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), 40 Convent Drive, Bethesda, MD 20892, USA. jmascola@nih.gov gary.nabel@sanofi.com.
authors.forename: John R
authors.initials: JR
authors.lastname: Mascola
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), 40 Convent Drive, Bethesda, MD 20892, USA. jmascola@nih.gov gary.nabel@sanofi.com.
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Nabel
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology / Q000627:therapeutic use*; D015704:CD4 Antigens / Q000276:immunology; D005260:Female; D015483:HIV Antibodies / Q000276:immunology / Q000627:therapeutic use; D015658:HIV Infections / Q000276:immunology* / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology*; D008253:Macaca mulatta; D008297:Male; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D015704:CD4 Antigens; D015483:HIV Antibodies; D054299:env Gene Products, Human Immunodeficiency Virus