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Molecular basis of SARS-CoV-2 Omicron variant evasion from shared neutralizing antibody response.
Patel, Anamika; Kumar, Sanjeev; Lai, Lilin; Chakravarthy, Chennareddy; Valanparambil, Rajesh; Reddy, Elluri Seetharami; Gottimukkala, Kamalvishnu; Bajpai, Prashant; Raju, Dinesh Ravindra; Edara, Venkata Viswanadh; Davis-Gardner, Meredith E; Linderman, Susanne; Dixit, Kritika; Sharma, Pragati; Mantus, Grace; Cheedarla, Narayanaiah; Verkerke, Hans P; Frank, Filipp; Neish, Andrew S; Roback, John D; Davis, Carl W; Wrammert, Jens; Ahmed, Rafi; Suthar, Mehul S; Sharma, Amit; Murali-Krishna, Kaja; Chandele, Anmol; Ortlund, Eric A.
  • 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.
  • 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.
  • 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.
  • 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.
  • Reddy ES; ICGEB-Emory Vaccine Center, International Center for Genetic Engineering and Biotechnology, New Delhi 110067, India; Kusuma School of Biological Sciences, Indian Institute of Technology, New Delhi 110016, India.
  • Gottimukkala K; ICGEB-Emory Vaccine Center, International Center for Genetic Engineering and Biotechnology, New Delhi 110067, India.
  • Bajpai P; ICGEB-Emory Vaccine Center, International Center for Genetic Engineering and Biotechnology, New Delhi 110067, India.
  • Raju DR; Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA; Georgia Tech, Atlanta, GA 30332, USA.
  • Edara VV; Department of Pediatrics, Division of Infectious Diseases, Emory University School of Medicine, Emory University, Atlanta, GA 30322, USA.
  • Davis-Gardner ME; Department of Pediatrics, Division of Infectious Diseases, Emory University School of Medicine, Emory University, Atlanta, GA 30322, USA.
  • Linderman S; 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.
  • Dixit K; ICGEB-Emory Vaccine Center, International Center for Genetic Engineering and Biotechnology, New Delhi 110067, India.
  • Sharma P; ICGEB-Emory Vaccine Center, International Center for Genetic Engineering and Biotechnology, New Delhi 110067, India.
  • Mantus G; 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.
  • Cheedarla N; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
  • Verkerke HP; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA; Department of Pathology, Brigham and Women's Hospital, Boston, MA 02215, USA.
  • Frank F; Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, 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.
  • 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,
  • Sharma A; Structural Parasitology Group, International Center for Genetic Engineering and Biotechnology, New Delhi 110067, India. Electronic address: amit.icgeb@gmail.com.
  • 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: chandeleanmol@gmail.com.
  • Ortlund EA; Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address: eortlun@emory.edu.
Structure ; 31(7): 801-811.e5, 2023 Jul 06.
Article in English | MEDLINE | ID: covidwho-2318034
ABSTRACT
Understanding the molecular features of neutralizing epitopes is important for developing vaccines/therapeutics against emerging SARS-CoV-2 variants. We describe three monoclonal antibodies (mAbs) generated from COVID-19 recovered individuals during the first wave of the pandemic in India. These mAbs had publicly shared near germline gene usage and potently neutralized Alpha and Delta, poorly neutralized Beta, and failed to neutralize Omicron BA.1 SARS-CoV-2 variants. Structural analysis of these mAbs in complex with trimeric spike protein showed that all three mAbs bivalently bind spike with two mAbs targeting class 1 and one targeting a class 4 receptor binding domain epitope. The immunogenetic makeup, structure, and function of these mAbs revealed specific molecular interactions associated with the potent multi-variant binding/neutralization efficacy. This knowledge shows how mutational combinations can affect the binding or neutralization of an antibody, which in turn relates to the efficacy of immune responses to emerging SARS-CoV-2 escape variants.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antibodies, Neutralizing / COVID-19 Topics: Vaccines / Variants Limits: Humans Language: English Journal: Structure Journal subject: Molecular Biology / Biochemistry / Biotechnology Year: 2023 Document Type: Article Affiliation country: J.str.2023.04.010

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antibodies, Neutralizing / COVID-19 Topics: Vaccines / Variants Limits: Humans Language: English Journal: Structure Journal subject: Molecular Biology / Biochemistry / Biotechnology Year: 2023 Document Type: Article Affiliation country: J.str.2023.04.010