Abstract

Some HIV infected patients develop potent antibody responses against HIV, but it is not clear how often this happens, nor how it occurs. We have undertaken a systemic evaluation of HIV+ sera to find those with broad neutralizing activity, understand how breadth of neutralization occurs and to isolate antibodies from the cells of such patients. We have observed that about 20% have broadly neutralizing antibodies. Among this group, we selected those patients with the broadest antibody response and have collected PBMC in order to isolate monoclonal antibodies. Our methodology includes isolating memory B-cells that are HIV-1 specific, and performing single cell PCR to isolate IgG genes. The genes are then cloned and expressed as full IgGs. To date, these approaches have yielded several novel anti-HIV monoclonal antibodies including VRC01 and VRC02 that neutralize 90% of HIV-1 strains. We have also performed 454 deep sequencing to study the clonal relationships and lineage of mAbs in these and other individuals.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAI005095-08
Application #
9161774
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
2015
Total Cost
Indirect Cost

  Institution

Name
Niaid Extramural Activities
Department
Type
DUNS #
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State
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  Publications

Kwon, Young D; Chuang, Gwo-Yu; Zhang, Baoshan et al. (2018) Surface-Matrix Screening Identifies Semi-specific Interactions that Improve Potency of a Near Pan-reactive HIV-1-Neutralizing Antibody. Cell Rep 22:1798-1809
Zhou, Tongqing; Zheng, Anqi; Baxa, Ulrich et al. (2018) A Neutralizing Antibody Recognizing Primarily N-Linked Glycan Targets the Silent Face of the HIV Envelope. Immunity 48:500-513.e6
Cale, Evan M; Gorman, Jason; Radakovich, Nathan A et al. (2017) Virus-like Particles Identify an HIV V1V2 Apex-Binding Neutralizing Antibody that Lacks a Protruding Loop. Immunity 46:777-791.e10
Huang, Jinghe; Kang, Byong H; Ishida, Elise et al. (2016) Identification of a CD4-Binding-Site Antibody to HIV that Evolved Near-Pan Neutralization Breadth. Immunity 45:1108-1121
Doria-Rose, Nicole A; Bhiman, Jinal N; Roark, Ryan S et al. (2016) New Member of the V1V2-Directed CAP256-VRC26 Lineage That Shows Increased Breadth and Exceptional Potency. J Virol 90:76-91
Kong, Rui; Xu, Kai; Zhou, Tongqing et al. (2016) Fusion peptide of HIV-1 as a site of vulnerability to neutralizing antibody. Science 352:828-33
Wu, Xueling; Zhang, Zhenhai; Schramm, Chaim A et al. (2015) Maturation and Diversity of the VRC01-Antibody Lineage over 15 Years of Chronic HIV-1 Infection. Cell 161:470-485
Zhou, Tongqing; Lynch, Rebecca M; Chen, Lei et al. (2015) Structural Repertoire of HIV-1-Neutralizing Antibodies Targeting the CD4 Supersite in 14 Donors. Cell 161:1280-92
Kong, Rui; Louder, Mark K; Wagh, Kshitij et al. (2015) Improving neutralization potency and breadth by combining broadly reactive HIV-1 antibodies targeting major neutralization epitopes. J Virol 89:2659-71
Doria-Rose, Nicole A; Schramm, Chaim A; Gorman, Jason et al. (2014) Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies. Nature 509:55-62

Showing the most recent 10 out of 47 publications