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

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 ()
Additional contact information
Shixia Wang: University of Massachusetts Chan Medical School
Kun-Wei Chan: New York University Grossman School of Medicine
Danlan Wei: National Institute of Allergy and Infectious Diseases, NIH
Xiuwen Ma: University of Massachusetts Chan Medical School
Shuying Liu: SYL Consulting
Guangnan Hu: University of Massachusetts Chan Medical School
Saeyoung Park: University of Massachusetts Chan Medical School
Ruimin Pan: New York University Grossman School of Medicine
Ying Gu: National Institute of Allergy and Infectious Diseases, NIH
Alexandra F. Nazzari: National Institute of Allergy and Infectious Diseases, NIH
Adam S. Olia: National Institute of Allergy and Infectious Diseases, NIH
Kai Xu: National Institute of Allergy and Infectious Diseases, NIH
Bob C. Lin: National Institute of Allergy and Infectious Diseases, NIH
Mark K. Louder: National Institute of Allergy and Infectious Diseases, NIH
Krisha McKee: National Institute of Allergy and Infectious Diseases, NIH
Nicole A. Doria-Rose: National Institute of Allergy and Infectious Diseases, NIH
David Montefiori: Duke University
Michael S. Seaman: Beth Israel Deaconess Medical Center, Harvard Medical School
Tongqing Zhou: National Institute of Allergy and Infectious Diseases, NIH
Peter D. Kwong: National Institute of Allergy and Infectious Diseases, NIH
James Arthos: National Institute of Allergy and Infectious Diseases, NIH
Xiang-Peng Kong: New York University Grossman School of Medicine
Shan Lu: University of Massachusetts Chan Medical School

Nature Communications, 2024, vol. 15, issue 1, 1-13

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.

Date: 2024
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DOI: 10.1038/s41467-024-48514-8

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