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Light chain of a public SARS-CoV-2 class-3 antibody modulates neutralization against Omicron.
Patel, Anamika; Kumar, Sanjeev; Lai, Lilin; Keen, Meredith; Valanparambil, Rajesh; Chakravarthy, Chennareddy; Laughlin, Zane; Frank, Filipp; Cheedarla, Narayanaiah; Verkerke, Hans P; Neish, Andrew S; Roback, John D; Davis, Carl W; Wrammert, Jens; Sharma, Amit; Ahmed, Rafi; Suthar, Mehul S; Murali-Krishna, Kaja; Chandele, Anmol; Ortlund, Eric.
  • Patel A; Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA.
  • Kumar S; ICGEB-Emory Vaccine Center, International Center for Genetic Engineering and Biotechnology, New Delhi 110067, India; Department of Pediatrics, Division of Infectious Diseases, Emory University School of Medicine, Emory University, Atlanta, GA 30322, USA; Emory Vaccine Center, Emory University, Atlan
  • Lai L; Department of Pediatrics, Division of Infectious Diseases, Emory University School of Medicine, Emory University, Atlanta, GA 30322, USA; Emory Vaccine Center, Emory University, Atlanta, GA 30322, USA.
  • Keen M; Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA.
  • Valanparambil R; Department of Microbiology and Immunology, Emory University School of Medicine, Emory University, Atlanta, GA 30322, USA; Emory Vaccine Center, Emory University, Atlanta, GA 30322, USA.
  • Chakravarthy C; Department of Microbiology and Immunology, Emory University School of Medicine, Emory University, Atlanta, GA 30322, USA; Emory Vaccine Center, Emory University, Atlanta, GA 30322, USA.
  • Laughlin Z; Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA.
  • Frank F; Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA.
  • Cheedarla N; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
  • Verkerke HP; Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
  • Neish AS; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
  • Roback JD; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
  • Davis CW; Department of Microbiology and Immunology, Emory University School of Medicine, Emory University, Atlanta, GA 30322, USA; Emory Vaccine Center, Emory University, Atlanta, GA 30322, USA.
  • Wrammert J; Department of Pediatrics, Division of Infectious Diseases, Emory University School of Medicine, Emory University, Atlanta, GA 30322, USA; Emory Vaccine Center, Emory University, Atlanta, GA 30322, USA.
  • Sharma A; Structural Parasitology Group, International Center for Genetic Engineering and Biotechnology, New Delhi 110067, India.
  • Ahmed R; Department of Microbiology and Immunology, Emory University School of Medicine, Emory University, Atlanta, GA 30322, USA; Emory Vaccine Center, Emory University, Atlanta, GA 30322, USA.
  • Suthar MS; Department of Pediatrics, Division of Infectious Diseases, Emory University School of Medicine, Emory University, Atlanta, GA 30322, USA; Department of Microbiology and Immunology, Emory University School of Medicine, Emory University, Atlanta, GA 30322, USA; Emory Vaccine Center, Emory University,
  • Murali-Krishna K; ICGEB-Emory Vaccine Center, International Center for Genetic Engineering and Biotechnology, New Delhi 110067, India; Department of Pediatrics, Division of Infectious Diseases, Emory University School of Medicine, Emory University, Atlanta, GA 30322, USA; Emory Vaccine Center, Emory University, Atlan
  • Chandele A; ICGEB-Emory Vaccine Center, International Center for Genetic Engineering and Biotechnology, New Delhi 110067, India. Electronic address: anmol@icgeb.res.in.
  • Ortlund E; Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address: eortlun@emory.edu.
Cell Rep ; 42(9): 113150, 2023 09 26.
Article en En | MEDLINE | ID: mdl-37708028
ABSTRACT
The pairing of antibody genes IGHV2-5/IGLV2-14 is established as a public immune response that potently cross-neutralizes SARS-CoV-2 variants, including Omicron, by targeting class-3/RBD-5 epitopes in the receptor binding domain (RBD). LY-CoV1404 (bebtelovimab) exemplifies this, displaying exceptional potency against Omicron sub-variants up to BA.5. Here, we report a human antibody, 002-S21B10, encoded by the public clonotype IGHV2-5/IGLV2-14. While 002-S21B10 neutralized key SARS-CoV-2 variants, it did not neutralize Omicron, despite sharing >92% sequence similarity with LY-CoV1404. The structure of 002-S21B10 in complex with spike trimer plus structural and sequence comparisons with LY-CoV1404 and other IGHV2-5/IGLV2-14 antibodies revealed significant variations in light-chain orientation, paratope residues, and epitope-paratope interactions that enable some antibodies to neutralize Omicron but not others. Confirming this, replacing the light chain of 002-S21B10 with the light chain of LY-CoV1404 restored 002-S21B10's binding to Omicron. Understanding such Omicron evasion from public response is vital for guiding therapeutics and vaccine design.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: SARS-CoV-2 / COVID-19 Límite: Humans Idioma: En Año: 2023 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Search on Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: SARS-CoV-2 / COVID-19 Límite: Humans Idioma: En Año: 2023 Tipo del documento: Article