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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.
- Authors
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.
- 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. Here the authors isolate monoclonal antibody HmAb64 from a healthy volunteer who received an experimental polyvalent DNA prime-protein boost HIV vaccine, and show that it's specific for the CD4 binding site and neutralizes cross-subtype HIV isolates including several tier-2 viruses.
- Subjects
MONOCLONAL antibodies; AIDS vaccines; HIV antibodies; DNA; VACCINES; BINDING sites; VENOM
- Publication
Nature Communications, 2024, Vol 15, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-024-48514-8