A single injection of anti-HIV-1 antibodies protects against repeated SHIV challenges.
Despite the success of potent anti-retroviral drugs in controlling human immunodeficiency virus type 1 (HIV-1) infection, little progress has been made in generating an effective HIV-1 vaccine. Although passive transfer of anti-HIV-1 broadly neutralizing antibodies can protect mice or macaques against a single high-dose challenge with HIV or simian/human (SIV/HIV) chimaeric viruses (SHIVs) respectively, the long-term efficacy of a passive antibody transfer approach for HIV-1 has not been examined. Here we show, on the basis of the relatively long-term protection conferred by hepatitis A immune globulin, the efficacy of a single injection (20 mg kg(-1)) of four anti-HIV-1-neutralizing monoclonal antibodies (VRC01, VRC01-LS, 3BNC117, and 10-1074 (refs 9 - 12)) in blocking repeated weekly low-dose virus challenges of the clade B SHIVAD8. Compared with control animals, which required two to six challenges (median = 3) for infection, a single broadly neutralizing antibody infusion prevented virus acquisition for up to 23 weekly challenges. This effect depended on antibody potency and half-life. The highest levels of plasma-neutralizing activity and, correspondingly, the longest protection were found in monkeys administered the more potent antibodies 3BNC117 and 10-1074 (median = 13 and 12.5 weeks, respectively). VRC01, which showed lower plasma-neutralizing activity, protected for a shorter time (median = 8 weeks). The introduction of a mutation that extends antibody half-life into the crystallizable fragment (Fc) domain of VRC01 increased median protection from 8 to 14.5 weeks. If administered to populations at high risk of HIV-1 transmission, such an immunoprophylaxis regimen could have a major impact on virus transmission.
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 USA.
Rajeev
R
Gautam
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 USA.
Yoshiaki
Y
Nishimura
Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892 USA; Biostatistics Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 USA.
Amarendra
A
Pegu
National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 USA; Biostatistics Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 USA.
Martha C
MC
Nason
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065 USA.|Laboratory of Experimental Immunology, Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931 Cologne, Germany.|Department I of Internal Medicine, Center of Integrated Oncology Cologne-Bonn, University Hospital Cologne, 50937 Cologne, Germany.
Florian
F
Klein
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065 USA.
Anna
A
Gazumyan
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065 USA.
Jovana
J
Golijanin
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 USA.
Alicia
A
Buckler-White
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 USA.
Reza
R
Sadjadpour
Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892 USA; Biostatistics Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 USA.
Keyun
K
Wang
Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892 USA; Biostatistics Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 USA.
Zachary
Z
Mankoff
Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892 USA; Biostatistics Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 USA.
Stephen D
SD
Schmidt
AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
Jeffrey D
JD
Lifson
Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892 USA; Biostatistics Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 USA.
John R
JR
Mascola
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065 USA.|Howard Hughes Medical Institute, Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931 Cologne, Germany.
Michel C
MC
Nussenzweig
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 USA.
Malcolm A
MA
Martin
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000097:blood / Q000235:genetics / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000008:administration & dosage / Q000097:blood / Q000235:genetics / Q000276:immunology; D005260:Female; D015483:HIV Antibodies / Q000008:administration & dosage* / Q000097:blood / Q000235:genetics / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control / Q000635:transmission; D006207:Half-Life; D007141:Immunoglobulin Fc Fragments / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D008253:Macaca mulatta / Q000276:immunology / Q000821:virology; D008297:Male; D009154:Mutation / Q000235:genetics; D017434:Protein Structure, Tertiary; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000276:immunology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000097:blood / Q000276:immunology* / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D013997:Time Factors
D016915:AIDS Vaccines; D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D007141:Immunoglobulin Fc Fragments; D018449:SAIDS Vaccines