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Distinct in vitro and in vivo neutralization profiles of monoclonal antibodies elicited by the receptor binding domain of the ancestral SARS-CoV-2.
Kwon, Hyung J; Zhang, Jun; Kosikova, Matina; Tang, Weichun; Ortega-Rodriguez, Uriel; Peng, Hanqin; Meseda, Clement A; Pedro, Cyntia L; Schmeisser, Falko; Lu, Jianming; Kang, Insung; Zhou, Bin; Davis, Charles T; Wentworth, David E; Chen, Wilbur H; Shriver, Mallory C; Barnes, Robin S; Pasetti, Marcela F; Weir, Jerry P; Chen, Bing; Xie, Hang.
  • Kwon HJ; Laboratory of Pediatric and Respiratory Viral Diseases, Division of Viral Products, Center for Biologics Evaluation and Research, Office of Vaccines Research and Review, United States Food and Drug Administration, Silver Spring, Maryland, USA.
  • Zhang J; Division of Molecular Medicine, Boston Children's Hospital, Boston, Massachusetts, USA.
  • Kosikova M; Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA.
  • Tang W; Laboratory of Pediatric and Respiratory Viral Diseases, Division of Viral Products, Center for Biologics Evaluation and Research, Office of Vaccines Research and Review, United States Food and Drug Administration, Silver Spring, Maryland, USA.
  • Ortega-Rodriguez U; Laboratory of Pediatric and Respiratory Viral Diseases, Division of Viral Products, Center for Biologics Evaluation and Research, Office of Vaccines Research and Review, United States Food and Drug Administration, Silver Spring, Maryland, USA.
  • Peng H; Laboratory of Pediatric and Respiratory Viral Diseases, Division of Viral Products, Center for Biologics Evaluation and Research, Office of Vaccines Research and Review, United States Food and Drug Administration, Silver Spring, Maryland, USA.
  • Meseda CA; Division of Molecular Medicine, Boston Children's Hospital, Boston, Massachusetts, USA.
  • Pedro CL; Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA.
  • Schmeisser F; Laboratory of DNA viruses, Division of Viral Products, Center for Biologics Evaluation and Research, Office of Vaccines Research and Review, United States Food and Drug Administration, Silver Spring, Maryland, USA.
  • Lu J; Laboratory of DNA viruses, Division of Viral Products, Center for Biologics Evaluation and Research, Office of Vaccines Research and Review, United States Food and Drug Administration, Silver Spring, Maryland, USA.
  • Kang I; Laboratory of DNA viruses, Division of Viral Products, Center for Biologics Evaluation and Research, Office of Vaccines Research and Review, United States Food and Drug Administration, Silver Spring, Maryland, USA.
  • Zhou B; Codex BioSolutions, Inc., Rockville, Maryland, USA.
  • Davis CT; Department of Biochemistry and Molecular and Cellular Biology, Georgetown University School of Medicine, Washington, District of Columbia, USA.
  • Wentworth DE; Laboratory of Pediatric and Respiratory Viral Diseases, Division of Viral Products, Center for Biologics Evaluation and Research, Office of Vaccines Research and Review, United States Food and Drug Administration, Silver Spring, Maryland, USA.
  • Chen WH; CDC COVID-19 Response, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
  • Shriver MC; CDC COVID-19 Response, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
  • Barnes RS; CDC COVID-19 Response, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
  • Pasetti MF; Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, USA.
  • Weir JP; Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, USA.
  • Chen B; Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, USA.
  • Xie H; Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, USA.
J Med Virol ; 95(3): e28673, 2023 03.
Article in English | MEDLINE | ID: covidwho-2267686
ABSTRACT
Broadly neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are sought to curb coronavirus disease 2019 (COVID-19) infections. Here we produced and characterized a set of mouse monoclonal antibodies (mAbs) specific for the ancestral SARS-CoV-2 receptor binding domain (RBD). Two of them, 17A7 and 17B10, were highly potent in microneutralization assay with 50% inhibitory concentration (IC50 ) ≤135 ng/mL against infectious SARS-CoV-2 variants, including G614, Alpha, Beta, Gamma, Delta, Epsilon, Zeta, Kappa, Lambda, B.1.1.298, B.1.222, B.1.5, and R.1. Both mAbs (especially 17A7) also exhibited strong in vivo efficacy in protecting K18-hACE2 transgenic mice from the lethal infection with G614, Alpha, Beta, Gamma, and Delta viruses. Structural analysis indicated that 17A7 and 17B10 target the tip of the receptor binding motif in the RBD-up conformation. A third RBD-reactive mAb (3A6) although escaped by Beta and Gamma, was highly effective in cross-neutralizing Delta and Omicron BA.1 variants in vitro and in vivo. In competition experiments, antibodies targeting epitopes similar to these 3 mAbs were rarely enriched in human COVID-19 convalescent sera or postvaccination sera. These results are helpful to inform new antibody/vaccine design and these mAbs can be useful tools for characterizing SARS-CoV-2 variants and elicited antibody responses.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 / Antibodies, Monoclonal Type of study: Randomized controlled trials Topics: Vaccines / Variants Limits: Animals / Humans Language: English Journal: J Med Virol Year: 2023 Document Type: Article Affiliation country: Jmv.28673

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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 / Antibodies, Monoclonal Type of study: Randomized controlled trials Topics: Vaccines / Variants Limits: Animals / Humans Language: English Journal: J Med Virol Year: 2023 Document Type: Article Affiliation country: Jmv.28673