• Drew Weissman, Mohamad-Gabriel Alameh, Thushan de Silva, Paul Collini, Hailey Hornsby, Rebecca Brown, Celia C LaBranche, Robert J Edwards, Laura Sutherland, Sampa Santra, Katayoun Mansouri, Sophie Gobeil, Charlene McDanal, Norbert Pardi, Nick Hengartner, Paulo J C Lin, Ying Tam, Pamela A Shaw, Mark G Lewis, Carsten Boesler, Uğur Şahin, Priyamvada Acharya, Barton F Haynes, Bette Korber, and David C Montefiori.
• Division of Infectious Diseases, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. Electronic address: dreww@pennmedicine.upenn.edu.
• Cell Host Microbe. 2021 Jan 13; 29 (1): 23-31.e4.

AbstractThe 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.Copyright © 2020. Published by Elsevier Inc.

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