D614G Spike Mutation Increases SARS CoV-2 Susceptibility to Neutralization
Author:
Weissman DrewORCID, 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, Şahin Uğur, Acharya Priyamvada, Haynes Barton F., Korber Bette, Montefiori David C.
Abstract
SummaryThe SARS-CoV-2 Spike protein acquired a D614G mutation early in the COVID-19 pandemic that appears to confer on the virus greater infectivity and is now the globally dominant form of the virus. Certain of the current vaccines entering phase 3 trials are based on the original D614 form of Spike with the goal of eliciting protective neutralizing antibodies. To determine whether D614G mediates 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 on their surface. In all cases, the G614 pseudovirus was moderately more susceptible to neutralization. The G614 pseudovirus also was more susceptible to neutralization by monoclonal antibodies against the receptor binding domain and by convalescent sera from people known to be infected with either the D614 or G614 form of the virus. These results indicate that a gain in infectivity provided by D614G came at the cost of making the virus more vulnerable to neutralizing antibodies, and that the mutation is not expected to be an obstacle for current vaccine development.
Publisher
Cold Spring Harbor Laboratory
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