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Human CD4-binding site antibody elicited by polyvalent DNA prime-protein boost vaccine neutralizes cross-clade tier-2-HIV strains.
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; Arthos, James; Kong, Xiang-Peng; Lu, Shan.
Afiliação
  • Wang S; Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, 01655, USA.
  • Chan KW; Department of Biochemistry and Molecular Pharmacology, New York University Grossman School of Medicine, New York, NY, 10016, USA.
  • Wei D; Laboratory of Immune Regulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, 20892, USA.
  • Ma X; Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, 01655, USA.
  • Liu S; SYL Consulting, Thousand Oak, CA, 91320, USA.
  • Hu G; Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, 01655, USA.
  • Park S; Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, 01655, USA.
  • Pan R; Department of Biochemistry and Molecular Pharmacology, New York University Grossman School of Medicine, New York, NY, 10016, USA.
  • Gu Y; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, 20892, USA.
  • Nazzari AF; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, 20892, USA.
  • Olia AS; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, 20892, USA.
  • Xu K; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, 20892, USA.
  • Lin BC; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, 20892, USA.
  • Louder MK; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, 20892, USA.
  • McKee K; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, 20892, USA.
  • Doria-Rose NA; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, 20892, USA.
  • Montefiori D; Department of Surgery, Duke University, Durham, NC, 27710, USA.
  • Seaman MS; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02115, USA.
  • Zhou T; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, 20892, USA.
  • Kwong PD; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, 20892, USA.
  • Arthos J; Laboratory of Immune Regulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, 20892, USA.
  • Kong XP; Department of Biochemistry and Molecular Pharmacology, New York University Grossman School of Medicine, New York, NY, 10016, USA.
  • Lu S; Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, 01655, USA. shan.lu@umassmed.edu.
Nat Commun ; 15(1): 4301, 2024 May 21.
Article em En | MEDLINE | ID: mdl-38773089
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Anticorpos Anti-HIV / Antígenos CD4 / HIV-1 / Vacinas contra a AIDS / Anticorpos Neutralizantes Limite: Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Anticorpos Anti-HIV / Antígenos CD4 / HIV-1 / Vacinas contra a AIDS / Anticorpos Neutralizantes Limite: Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article