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-Structure paper
タイトル | Human CD4-binding site antibody elicited by polyvalent DNA prime-protein boost vaccine neutralizes cross-clade tier-2-HIV strains. |
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ジャーナル・号・ページ | Nat Commun, Vol. 15, Issue 1, Page 4301, Year 2024 |
掲載日 | 2024年5月21日 |
著者 | 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 / Krisha McKee / Nicole A Doria-Rose / David Montefiori / Michael S Seaman / Tongqing Zhou / Peter D Kwong / James Arthos / Xiang-Peng Kong / Shan Lu / |
PubMed 要旨 | 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, ...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. |
リンク | Nat Commun / PubMed:38773089 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.74 Å |
構造データ | EMDB-41569, PDB-8tr3: |
化合物 | ChemComp-NAG: |
由来 |
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キーワード | IMMUNE SYSTEM/VIRAL PROTEIN / HIV / Env / glycoprotein / mAb / IMMUNE SYSTEM / IMMUNE SYSTEM-VIRAL PROTEIN complex |