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TitleHuman CD4-binding site antibody elicited by polyvalent DNA prime-protein boost vaccine neutralizes cross-clade tier-2-HIV strains.
Journal, issue, pagesNat Commun, Vol. 15, Issue 1, Page 4301, Year 2024
Publish dateMay 21, 2024
AuthorsShixia 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 / Shan Lu /
PubMed AbstractThe 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, ...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.
External linksNat Commun / PubMed:38773089 / PubMed Central
MethodsEM (single particle)
Resolution3.74 Å
Structure data

EMDB-41569, PDB-8tr3:
Cryo-EM structure of HmAb64 scFv in complex with CNE40 SOSIP trimer
Method: EM (single particle) / Resolution: 3.74 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • homo sapiens (human)
  • human immunodeficiency virus 1
KeywordsIMMUNE SYSTEM/VIRAL PROTEIN / HIV / Env / glycoprotein / mAb / IMMUNE SYSTEM / IMMUNE SYSTEM-VIRAL PROTEIN complex

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