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 individuals.

Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Zip Code
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
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
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 161:470-85
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
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
Mascola, John R; Haynes, Barton F (2013) HIV-1 neutralizing antibodies: understanding nature's pathways. Immunol Rev 254:225-44
Zhou, Tongqing; Zhu, Jiang; Wu, Xueling et al. (2013) Multidonor analysis reveals structural elements, genetic determinants, and maturation pathway for HIV-1 neutralization by VRC01-class antibodies. Immunity 39:245-58
Kwong, Peter D; Mascola, John R; Nabel, Gary J (2013) Broadly neutralizing antibodies and the search for an HIV-1 vaccine: the end of the beginning. Nat Rev Immunol 13:693-701
Zhu, Jiang; Ofek, Gilad; Yang, Yongping et al. (2013) Mining the antibodyome for HIV-1-neutralizing antibodies with next-generation sequencing and phylogenetic pairing of heavy/light chains. Proc Natl Acad Sci U S A 110:6470-5

Showing the most recent 10 out of 38 publications