Human CD4-binding site antibody elicited by polyvalent DNA prime-protein boost vaccine neutralizes cross-clade tier-2-HIV strains

Wang, Shixia; Chan, Kun-Wei; Wei, Danlan; Ma, Xiuwen; Liu, Shuying; Hu, Guangnan; Park, Saeyoung; Pan, Ruimin; Gu, Ying; Nazzari, Alexandra F.; Olia, Adam S.; Xu, Kai; Lin, Bob C.; Louder, Mark K.; McKee, Krisha; Doria-Rose, Nicole A.; Montefiori, David; Seaman, Michael S.; Zhou, Tongqing; Kwong, Peter D.; Arthos, James; Kong, Xiang-Peng; Lu, Shan

doi:10.1038/s41467-024-48514-8

Title: Human CD4-binding site antibody elicited by polyvalent DNA prime-protein boost vaccine neutralizes cross-clade tier-2-HIV strains

Journal Article · 21 May 2024 · Nature Communications

DOI: https://doi.org/10.1038/s41467-024-48514-8 · OSTI ID:2470333

^[1];

^[2]; Wei, Danlan ^[3]; Ma, Xiuwen ^[1]; Liu, Shuying ^[4]; Hu, Guangnan ^[1]; Park, Saeyoung ^[1]; Pan, Ruimin ^[2]; Gu, Ying ^[3]; Nazzari, Alexandra F. ^[3]; Olia, Adam S. ^[3]; Xu, Kai ^[3]; Lin, Bob C. ^[3];

^[3]; McKee, Krisha ^[3];

^[3];

^[5]; Seaman, Michael S. ^[6];

^[3];

^[3] more »

Univ. of Massachusetts, Worcester, MA (United States). Chan Medical School
New York Univ. (NYU), NY (United States). Grossman School of Medicine
National Institutes of Health (NIH), Bethesda, MD (United States)
SYL Consulting, Thousand Oak, CA (United States)
Duke Univ., Durham, NC (United States)
Harvard Medical School, Boston, MA (United States)

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.

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Research Organization:: Brookhaven National Laboratory (BNL), Upton, NY (United States). National Synchrotron Light Source II (NSLS-II)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: SC0012704

OSTI ID:: 2470333

Journal Information:: Nature Communications, Journal Name: Nature Communications Journal Issue: 1 Vol. 15; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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Title: Human CD4-binding site antibody elicited by polyvalent DNA prime-protein boost vaccine neutralizes cross-clade tier-2-HIV strains

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