Passive transfer of modest titers of potent and broadly neutralizing anti-HIV monoclonal antibodies block SHIV infection in macaques

• Published in: The Journal of experimental medicine Vol. 211; no. 10; pp. 2061 - 2074
• Main Authors: Shingai, Masashi, Donau, Olivia K., Plishka, Ronald J., Buckler-White, Alicia, Mascola, John R., Nabel, Gary J., Nason, Martha C., Montefiori, David, Moldt, Brian, Poignard, Pascal, Diskin, Ron, Bjorkman, Pamela J., Eckhaus, Michael A., Klein, Florian, Mouquet, Hugo, Cetrulo Lorenzi, Julio Cesar, Gazumyan, Anna, Burton, Dennis R., Nussenzweig, Michel C., Martin, Malcolm A., Nishimura, Yoshiaki
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 22.09.2014
• Subjects: Animals; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - immunology; Antibodies, Neutralizing - administration & dosage; Antibodies, Neutralizing - immunology; DNA Primers - genetics; HIV - immunology; HIV Antibodies - administration & dosage; HIV Antibodies - immunology; Human immunodeficiency virus; Humans; Lentivirus Infections - prevention & control; Macaca mulatta; Mutagenesis; Neutralization Tests; Regression Analysis; Simian immunodeficiency virus; Simian Immunodeficiency Virus - immunology; Swine influenza virus; Vaccination - methods
• ISSN: 0022-1007; 1540-9538; 1540-9538
• DOI: 10.1084/jem.20132494

It is widely appreciated that effective human vaccines directed against viral pathogens elicit neutralizing antibodies (NAbs). The passive transfer of anti–HIV-1 NAbs conferring sterilizing immunity to macaques has been used to determine the plasma neutralization titers, which must be present at the time of exposure, to prevent acquisition of SIV/HIV chimeric virus (SHIV) infections. We administered five recently isolated potent and broadly acting anti-HIV neutralizing monoclonal antibodies (mAbs) to rhesus macaques and challenged them intrarectally 24 h later with either of two different R5-tropic SHIVs. By combining the results obtained from 60 challenged animals, we determined that the protective neutralization titer in plasma preventing virus infection in 50% of the exposed monkeys was relatively modest (∼1:100) and potentially achievable by vaccination.