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

Author

Listed:
  • 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)

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.

Suggested Citation

  • 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 & Kr, 2024. "Human CD4-binding site antibody elicited by polyvalent DNA prime-protein boost vaccine neutralizes cross-clade tier-2-HIV strains," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48514-8
    DOI: 10.1038/s41467-024-48514-8
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