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

Author:

Shingai Masashi1,Donau Olivia K.1,Plishka Ronald J.1,Buckler-White Alicia1,Mascola John R.1,Nabel Gary J.1,Nason Martha C.1,Montefiori David2,Moldt Brian333,Poignard Pascal333,Diskin Ron4,Bjorkman Pamela J.56,Eckhaus Michael A.7,Klein Florian8,Mouquet Hugo9,Cetrulo Lorenzi Julio Cesar8,Gazumyan Anna8,Burton Dennis R.33310,Nussenzweig Michel C.68,Martin Malcolm A.1,Nishimura Yoshiaki1

Affiliation:

1. Laboratory of Molecular Microbiology, Virology Laboratory, Vaccine Research Center, and Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892

2. Department of Surgery, Duke University Medical Center, Durham, NC 27710

3. Department of Immunology and Microbial Science, IAVI Neutralizing Antibody Center, and Center for HIV/AIDS Vaccine immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037

4. Department of Structural Biology, Weizmann Institute of Science, Rehovot 7610001, Israel

5. Division of Biology, California Institute of Technology, Pasadena, CA 91125

6. Howard Hughes Medical Institute, Chevy Chase, MD 20815

7. Diagnostic and Research Services Branch, Office of the Director, National Institutes of Health, Bethesda, MD 20892

8. Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065

9. Laboratory of Humoral Response to Pathogens, Department of Immunology, Institut Pasteur, 75724 Paris, France

10. Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard, Boston, MA 021142

Abstract

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.

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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