8TR3

Cryo-EM structure of HmAb64 scFv in complex with CNE40 SOSIP trimer

Summary for 8TR3

• Entry DOI: 10.2210/pdb8tr3/pdb
• EMDB information: 41569
• Descriptor: CNE40 SOSIP Envelope glycoprotein gp120, CNE40 SOSIP Transmembrane protein gp41, HmAb64 Fv heavy chain, ... (6 entities in total)
• Functional Keywords: hiv, env, glycoprotein, mab, immune system, immune system-viral protein complex, immune system/viral protein
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 12
• Total formula weight: 301983.21

Authors

Chan, K.-W.,Kong, X.P. (deposition date: 2023-08-09, release date: 2024-06-19, Last modification date: 2024-11-06)

Primary citation

Wang, S.,Chan, K.W.,Wei, D.,Ma, X.,Liu, S.,Hu, G.,Park, S.,Pan, R.,Gu, Y.,Nazzari, A.F.,Olia, A.S.,Xu, K.,Lin, B.C.,Louder, M.K.,McKee, K.,Doria-Rose, N.A.,Montefiori, D.,Seaman, M.S.,Zhou, T.,Kwong, P.D.,Arthos, J.,Kong, X.P.,Lu, S.
Human CD4-binding site antibody elicited by polyvalent DNA prime-protein boost vaccine neutralizes cross-clade tier-2-HIV strains.
Nat Commun, 15:4301-4301, 2024

PubMed 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.

PubMed: 38773089
DOI: 10.1038/s41467-024-48514-8

Experimental method

ELECTRON MICROSCOPY (3.74 Å)