Publication Date:
2013-11-01
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4133787/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4133787/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shingai, Masashi -- Nishimura, Yoshiaki -- Klein, Florian -- Mouquet, Hugo -- Donau, Olivia K -- Plishka, Ronald -- Buckler-White, Alicia -- Seaman, Michael -- Piatak, Michael Jr -- Lifson, Jeffrey D -- Dimitrov, Dimiter S -- Nussenzweig, Michel C -- Martin, Malcolm A -- HHSN261200800001E/PHS HHS/ -- P01 AI100148/AI/NIAID NIH HHS/ -- ZIA AI000415-29/Intramural NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2013 Nov 14;503(7475):277-80. doi: 10.1038/nature12746. Epub 2013 Oct 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA [2].〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24172896" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Antibodies, Neutralizing/*therapeutic use
;
Antigens, CD4/metabolism
;
Binding Sites/immunology
;
HIV Antibodies/*therapeutic use
;
HIV Envelope Protein gp120/immunology
;
HIV-1/*immunology
;
*Immunotherapy
;
Macaca/immunology
;
Molecular Sequence Data
;
Peptide Fragments/immunology
;
Simian Acquired Immunodeficiency Syndrome/prevention & control/*therapy
;
Simian Immunodeficiency Virus/*physiology
;
Time Factors
;
Viral Load
;
Viremia/*therapy
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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