title: Antibody-mediated immunotherapy of macaques chronically infected with SHIV suppresses viraemia.
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.
authors.affiliation: 1] Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA [2].
authors.forename: Masashi
authors.initials: M
authors.lastname: Shingai
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Nishimura
authors.forename: Florian
authors.initials: F
authors.lastname: Klein
authors.forename: Hugo
authors.initials: H
authors.lastname: Mouquet
authors.forename: Olivia K
authors.initials: OK
authors.lastname: Donau
authors.forename: Ronald
authors.initials: R
authors.lastname: Plishka
authors.forename: Alicia
authors.initials: A
authors.lastname: Buckler-White
authors.forename: Michael
authors.initials: M
authors.lastname: Seaman
authors.forename: Michael
authors.initials: M
authors.lastname: Piatak
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Lifson
authors.forename: Dimiter S
authors.initials: DS
authors.lastname: Dimitrov
authors.forename: Michel C
authors.initials: MC
authors.lastname: Nussenzweig
authors.forename: Malcolm A
authors.initials: MA
authors.lastname: Martin
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000627:therapeutic use*; D001665:Binding Sites / Q000276:immunology; D015704:CD4 Antigens / Q000378:metabolism; D015483:HIV Antibodies / Q000627:therapeutic use*; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D007167:Immunotherapy; D008251:Macaca / Q000276:immunology; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control / Q000628:therapy*; D015302:Simian Immunodeficiency Virus / Q000502:physiology*; D013997:Time Factors; D019562:Viral Load; D014766:Viremia / Q000628:therapy*
chemical_list: D057134:Antibodies, Neutralizing; D015704:CD4 Antigens; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments