Antibody-mediated immunotherapy of macaques chronically infected with SHIV suppresses viraemia

• Published in: Nature (London) Vol. 503; no. 7475; pp. 277 - 280
• Main Authors: Shingai, Masashi, Nishimura, Yoshiaki, Klein, Florian, Mouquet, Hugo, Donau, Olivia K., Plishka, Ronald, Buckler-White, Alicia, Seaman, Michael, Piatak, Michael, Lifson, Jeffrey D., Dimitrov, Dimiter, Nussenzweig, Michel C., Martin, Malcolm A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 14.11.2013; Nature Publishing Group
• Subjects: 13/1; 13/106; 13/31; 631/250/255/1901; Animals; Antibodies; Antibodies, Neutralizing - therapeutic use; Antiretroviral agents; Antiretroviral drugs; Binding sites; Binding Sites - immunology; CD4 Antigens - metabolism; Cloning; Drug dosages; HIV; HIV (Viruses); HIV Antibodies - therapeutic use; HIV Envelope Protein gp120 - immunology; HIV-1 - immunology; Human immunodeficiency virus; Humanities and Social Sciences; Immune system; Immunotherapy; Infections; letter; Macaca - immunology; Medical research; Medicine, Experimental; Molecular Sequence Data; Monoclonal antibodies; multidisciplinary; Neutralization; Peptide Fragments - immunology; Physiological aspects; Plasma; Science; Simian Acquired Immunodeficiency Syndrome - prevention & control; Simian Acquired Immunodeficiency Syndrome - therapy; Simian Immunodeficiency Virus - physiology; Time Factors; Viral antibodies; Viral Load; Viremia; Viremia - therapy; United States
• ISSN: 0028-0836; 1476-4687; 1476-4687
• DOI: 10.1038/nature12746

A new generation of broad and potent anti-HIV-1 monoclonal antibodies has recently been isolated; co-administration of two such antibodies is shown here to result in rapid and potent suppression of plasma viraemia in five chronically SHIV-infected macaques that lasts for several weeks. Monoclonal antibodies in HIV therapy Two papers published this week test the new generation of broad and potent anti-HIV1 monoclonal antibodies (mAbs) in primate models with promising results, both concluding that their results strongly encourage the investigation of mAb therapy for HIV-1 in humans. Dan Barouch et al . show that a single infusion of the potent, broadly neutralizing anti-HIV-1 antibody PGT121, as well as various mAb cocktails, suppress the virus to undetectable levels in just a week in SHIV-infected rhesus monkeys. Masashi Shingai et al . report that co-administration of the antibodies 3BNC117 and 10-1074 results in potent suppression of plasma viraemia lasting for several weeks in chronically SHIV-infected macaques. Neutralizing antibodies can confer immunity to primate lentiviruses by blocking infection in macaque models of AIDS 1 , 2 , 3 , 4 . However, earlier studies of anti-human immunodeficiency virus type 1 (HIV-1) neutralizing antibodies administered to infected individuals or humanized mice reported poor control of virus replication and the rapid emergence of resistant variants 5 , 6 , 7 . A new generation of anti-HIV-1 monoclonal antibodies, possessing extraordinary potency and breadth of neutralizing activity, has recently been isolated from infected individuals 8 . These neutralizing antibodies target different regions of the HIV-1 envelope glycoprotein including the CD4-binding site, glycans located in the V1/V2, V3 and V4 regions, and the membrane proximal external region of gp41 (refs 9 , 10 , 11 , 12 , 13 , 14 ). Here we have examined two of the new antibodies, directed to the CD4-binding site and the V3 region (3BNC117 and 10-1074, respectively), for their ability to block infection and suppress viraemia in macaques infected with the R5 tropic simian–human immunodeficiency virus (SHIV)-AD8, which emulates many of the pathogenic and immunogenic properties of HIV-1 during infections of rhesus macaques 15 , 16 . Either antibody alone can potently block virus acquisition. When administered individually to recently infected macaques, the 10-1074 antibody caused a rapid decline in virus load to undetectable levels for 4–7 days, followed by virus rebound during which neutralization-resistant variants became detectable. When administered together, a single treatment rapidly suppressed plasma viraemia for 3–5 weeks in some long-term chronically SHIV-infected animals with low CD4 + T-cell levels. A second cycle of anti-HIV-1 monoclonal antibody therapy, administered to two previously treated animals, successfully controlled virus rebound. These results indicate that immunotherapy or a combination of immunotherapy plus conventional antiretroviral drugs might be useful as a treatment for chronically HIV-1-infected individuals experiencing immune dysfunction.