1. Human CD4-binding site antibody elicited by polyvalent DNA prime-protein boost vaccine neutralizes cross-clade tier-2-HIV strains
- Author
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Shixia Wang, Kun-Wei Chan, Danlan Wei, Xiuwen Ma, Shuying Liu, Guangnan Hu, Saeyoung Park, Ruimin Pan, Ying Gu, Alexandra F. Nazzari, Adam S. Olia, Kai Xu, Bob C. Lin, Mark K. Louder, Krisha McKee, Nicole A. Doria-Rose, David Montefiori, Michael S. Seaman, Tongqing Zhou, Peter D. Kwong, James Arthos, Xiang-Peng Kong, and Shan Lu
- Subjects
Science - Abstract
Abstract The vaccine elicitation of HIV tier-2-neutralization antibodies has been a challenge. Here, we report the isolation and characterization of a CD4-binding site (CD4bs) specific monoclonal antibody, HmAb64, from a human volunteer immunized with a polyvalent DNA prime-protein boost HIV vaccine. HmAb64 is derived from heavy chain variable germline gene IGHV1-18 and light chain germline gene IGKV1-39. It has a third heavy chain complementarity-determining region (CDR H3) of 15 amino acids. On a cross-clade panel of 208 HIV-1 pseudo-virus strains, HmAb64 neutralized 20 (10%), including tier-2 strains from clades B, BC, C, and G. The cryo-EM structure of the antigen-binding fragment of HmAb64 in complex with a CNE40 SOSIP trimer revealed details of its recognition; HmAb64 uses both heavy and light CDR3s to recognize the CD4-binding loop, a critical component of the CD4bs. This study demonstrates that a gp120-based vaccine can elicit antibodies capable of tier 2-HIV neutralization.
- Published
- 2024
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