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D614G Spike Mutation Increases SARS CoV-2 Susceptibility to Neutralization.
Weissman, Drew; Alameh, Mohamad-Gabriel; de Silva, Thushan; Collini, Paul; Hornsby, Hailey; Brown, Rebecca; LaBranche, Celia C; Edwards, Robert J; Sutherland, Laura; Santra, Sampa; Mansouri, Katayoun; Gobeil, Sophie; McDanal, Charlene; Pardi, Norbert; Hengartner, Nick; Lin, Paulo J C; Tam, Ying; Shaw, Pamela A; Lewis, Mark G; Boesler, Carsten; Sahin, Ugur; Acharya, Priyamvada; Haynes, Barton F; Korber, Bette; Montefiori, David C.
  • Weissman D; Division of Infectious Diseases, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. Electronic address: dreww@pennmedicine.upenn.edu.
  • Alameh MG; Division of Infectious Diseases, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
  • de Silva T; Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK; South Yorkshire Regional Department of Infection and Tropical Medicine, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.
  • Collini P; Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK; South Yorkshire Regional Department of Infection and Tropical Medicine, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.
  • Hornsby H; Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK.
  • Brown R; Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK.
  • LaBranche CC; Department of Surgery, Duke University School of Medicine, Durham, NC, USA.
  • Edwards RJ; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA; Duke University, Department of Medicine, Durham, NC, USA.
  • Sutherland L; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
  • Santra S; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
  • Mansouri K; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
  • Gobeil S; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
  • McDanal C; Department of Surgery, Duke University School of Medicine, Durham, NC, USA.
  • Pardi N; Division of Infectious Diseases, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
  • Hengartner N; T6: Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM USA.
  • Lin PJC; Acuitas Therapeutics, Vancouver, BC, CA.
  • Tam Y; Acuitas Therapeutics, Vancouver, BC, CA.
  • Shaw PA; Department of Biostatistics, Epidemiology and Informatics University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
  • Lewis MG; Bioqual Inc., Rockville, MD, USA.
  • Boesler C; BioNTech, Mainz, Germany.
  • Sahin U; BioNTech, Mainz, Germany.
  • Acharya P; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
  • Haynes BF; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
  • Korber B; T6: Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM USA.
  • Montefiori DC; Department of Surgery, Duke University School of Medicine, Durham, NC, USA; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
Cell Host Microbe ; 29(1): 23-31.e4, 2021 01 13.
Article in English | MEDLINE | ID: covidwho-956078
Preprint
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ABSTRACT
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein acquired a D614G mutation early in the pandemic that confers greater infectivity and is now the globally dominant form. To determine whether D614G might also mediate neutralization escape that could compromise vaccine efficacy, sera from spike-immunized mice, nonhuman primates, and humans were evaluated for neutralization of pseudoviruses bearing either D614 or G614 spike. In all cases, the G614 pseudovirus was moderately more susceptible to neutralization. The G614 pseudovirus also was more susceptible to neutralization by receptor-binding domain (RBD) monoclonal antibodies and convalescent sera from people infected with either form of the virus. Negative stain electron microscopy revealed a higher percentage of the 1-RBD "up" conformation in the G614 spike, suggesting increased epitope exposure as a mechanism of enhanced vulnerability to neutralization. Based on these findings, the D614G mutation is not expected to be an obstacle for current vaccine development.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Spike Glycoprotein, Coronavirus / SARS-CoV-2 / COVID-19 / Mutation Type of study: Experimental Studies / Randomized controlled trials Topics: Vaccines Limits: Adolescent / Adult / Animals / Female / Humans / Male / Middle aged / Young adult Language: English Journal: Cell Host Microbe Journal subject: Microbiology Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Spike Glycoprotein, Coronavirus / SARS-CoV-2 / COVID-19 / Mutation Type of study: Experimental Studies / Randomized controlled trials Topics: Vaccines Limits: Adolescent / Adult / Animals / Female / Humans / Male / Middle aged / Young adult Language: English Journal: Cell Host Microbe Journal subject: Microbiology Year: 2021 Document Type: Article