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

• Published in: Nature (London) Vol. 533; no. 7601; pp. 105 - 109
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05.05.2016; Nature Publishing Group
• Subjects: 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
• ISSN: 0028-0836; 1476-4687; 1476-4687
• DOI: 10.1038/nature17677

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.