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Human CD4-Binding Site Antibody Elicited by Polyvalent DNA Prime-Protein Boost Vaccine Neutralizes Cross-Clade Tier-2-HIV Strains.
- Source :
-
Research square [Res Sq] 2023 Oct 20. Date of Electronic Publication: 2023 Oct 20. - Publication Year :
- 2023
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Abstract
- The vaccine elicitation of HIV-neutralizing antibodies with tier-2-neutralization breadth has been a challenge. Here, we report the isolation and characteristics of a CD4-binding site specific monoclonal antibody, HmAb64, from a human volunteer immunized with a polyvalent gp120 DNA prime-protein boost vaccine. HmAb64 derived from heavy chain variable germline gene IGHV1-18, light chain germline gene IGKV1-39, and had a 3 <superscript>rd</superscript> 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 21 (10%), including tier-2 neutralization resistant strains from clades B, BC, C, and G. The cryo-EM structure of the antigen-binding fragment of HmAb64 bound to a conformation between prefusion closed and occluded open forms of envelope trimer, using both heavy and light CDR3s to recognize the CD4-binding loop, a critical component of the CD4-binding site. A gp120 subunit-based vaccine can thus elicit an antibody capable of tier 2-HIV neutralization.<br />Competing Interests: Conflict of interest: Patents related to PDPHV were licensed by the University of Massachusetts Medical School to Worcester HIV Vaccine (WHV), a private biotech company dedicated to HIV vaccine product development.
Details
- Language :
- English
- Database :
- MEDLINE
- Journal :
- Research square
- Accession number :
- 37886518
- Full Text :
- https://doi.org/10.21203/rs.3.rs-3360161/v1