Journal Article

A single injection of anti-HIV-1 antibodies protects against repeated SHIV challenges

Nussenzweig, Michel C., Lifson, Jeffrey D., Pegu, Amarendra, Gazumyan, Anna, Wang, Keyun, Martin, Malcolm A., Mascola, John R., Buckler-White, Alicia, Nishimura, Yoshiaki, Sadjadpour, Reza, Mankoff, Zachary, Gautam, Rajeev, Nason, Martha C., Golijanin, Jovana, Klein, Florian, Schmidt, Stephen D.

2016

Overview

A single injection of four anti-HIV-1-neutralizing monoclonal antibodies blocks repeated weekly low-dose virus challenges of simian/human immunodeficiency virus. Immunoprophylaxis against HIV-1 infection This study assesses the long-term efficacy of a passive antibody transfer approach for the control of human immunodeficiency virus type 1 (HIV-1) infection. Malcolm Martin and colleagues administered single intravenous injections of four different anti-HIV-1 neutralizing monoclonal antibodies in a simian/HIV intrarectal exposure model involving weekly low-dose viral challenge and demonstrate protection from infection lasting almost 6 months. 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 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 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 , 10 , 11 , 12 )) in blocking repeated weekly low-dose virus challenges of the clade B SHIV AD8 . 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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 13 / 13/1 / 13/106 / 13/109 / 13/31 / 631/326/596/1787 / 64 / 692/699/255/1901 / AIDS Vaccines - administration & dosage / AIDS Vaccines - immunology / Animals / Antibodies / Antibodies, Monoclonal - administration & dosage / Antibodies, Monoclonal - blood / Antibodies, Monoclonal - genetics / Antibodies, Monoclonal - immunology / Antibodies, Neutralizing - administration & dosage / Antibodies, Neutralizing - blood / Antibodies, Neutralizing - genetics / Antibodies, Neutralizing - immunology / Dosage and administration / Female / Half-Life / HIV / HIV Antibodies - administration & dosage / HIV Antibodies - blood / HIV Antibodies - genetics / HIV Antibodies - immunology / HIV infection / HIV Infections - immunology / HIV Infections - prevention & control / HIV Infections - transmission / Human immunodeficiency virus / Humanities and Social Sciences / Immunization / Immunoglobulin Fc Fragments - chemistry / Immunoglobulin Fc Fragments - genetics / Immunoglobulin Fc Fragments - immunology / Immunoglobulins / Injection / letter / Macaca mulatta - immunology / Macaca mulatta - virology / Male / Monoclonal antibodies / multidisciplinary / Mutation - genetics / Patient outcomes / Prevention / Protein Structure, Tertiary / SAIDS Vaccines - administration & dosage / SAIDS Vaccines - immunology / Science / Simian Acquired Immunodeficiency Syndrome - blood / Simian Acquired Immunodeficiency Syndrome - immunology / Simian Acquired Immunodeficiency Syndrome - prevention & control / Simian Immunodeficiency Virus - immunology / Time Factors / Vaccines / Viral antibodies / Viral infections