Publication Date:
2016-04-28
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gautam, Rajeev -- Nishimura, Yoshiaki -- Pegu, Amarendra -- Nason, Martha C -- Klein, Florian -- Gazumyan, Anna -- Golijanin, Jovana -- Buckler-White, Alicia -- Sadjadpour, Reza -- Wang, Keyun -- Mankoff, Zachary -- Schmidt, Stephen D -- Lifson, Jeffrey D -- Mascola, John R -- Nussenzweig, Michel C -- Martin, Malcolm A -- AI-100148/AI/NIAID NIH HHS/ -- HHSN261200800001E/PHS HHS/ -- UM1 AI100663-01/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- Intramural NIH HHS/ -- England -- Nature. 2016 May 5;533(7601):105-9. doi: 10.1038/nature17677. Epub 2016 Apr 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. ; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. ; Biostatistics Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. ; Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 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. ; AIDS and Cancer Virus Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland 21702, USA. ; Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27120156" target="_blank"〉PubMed〈/a〉
Keywords:
AIDS Vaccines/administration & dosage/immunology
;
Animals
;
Antibodies, Monoclonal/administration & dosage/blood/genetics/immunology
;
Antibodies, Neutralizing/administration & dosage/blood/genetics/immunology
;
Female
;
HIV Antibodies/*administration & dosage/blood/genetics/*immunology
;
HIV Infections/immunology/prevention & control/transmission
;
Half-Life
;
Immunoglobulin Fc Fragments/chemistry/genetics/immunology
;
Macaca mulatta/immunology/virology
;
Male
;
Mutation/genetics
;
Protein Structure, Tertiary
;
SAIDS Vaccines/administration & dosage/immunology
;
Simian Acquired Immunodeficiency Syndrome/blood/*immunology/*prevention & control
;
Simian Immunodeficiency Virus/*immunology
;
Time Factors
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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