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

TitleAntibody-mediated immunotherapy of macaques chronically infected with SHIV suppresses viraemia.
Publication TypeJournal Article
Year of Publication2013
AuthorsShingai M, Nishimura Y, Klein F, Mouquet H, Donau OK, Plishka R, Buckler-White A, Seaman M, Piatak M, Lifson JD, Dimitrov DS, Nussenzweig MC, Martin MA
JournalNature
Volume503
Issue7475
Pagination277-80
Date Published11/14/2013
ISSN1476-4687
KeywordsAnimals, Antibodies, Neutralizing, Antigens, CD4, Binding Sites, HIV Antibodies, HIV Envelope Protein gp120, HIV-1, Immunotherapy, Macaca, Molecular Sequence Data, Peptide Fragments, Simian Acquired Immunodeficiency Syndrome, Simian immunodeficiency virus, Time Factors, Viral Load, Viremia
Abstract

Neutralizing antibodies can confer immunity to primate lentiviruses by blocking infection in macaque models of AIDS. 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. A new generation of anti-HIV-1 monoclonal antibodies, possessing extraordinary potency and breadth of neutralizing activity, has recently been isolated from infected individuals. 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 9-14). 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. 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.

DOI10.1038/nature12746
Alternate JournalNature
PubMed ID24172896
Grant ListHHSN261200800001E / / PHS HHS / United States
P01 AI100148 / AI / NIAID NIH HHS / United States
/ / Howard Hughes Medical Institute / United States
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