D614G Spike Mutation Increases SARS CoV-2 Susceptibility to Neutralization.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Weissman, D; Alameh, M-G; de Silva, T; Collini, P; Hornsby, H; Brown, R; LaBranche, CC; Edwards, RJ; Sutherland, L; Santra, S; Mansouri, K; Gobeil, S; McDanal, C; Pardi, N; Hengartner, N; Lin, PJC; Tam, Y; Shaw, PA; Lewis, MG; Boesler, C; ┼×ahin, U; Acharya, P; Haynes, BF; Korber, B; Montefiori, DC

Published Date

  • January 13, 2021

Published In

Volume / Issue

  • 29 / 1

Start / End Page

  • 23 - 31.e4

PubMed ID

  • 33306985

Pubmed Central ID

  • PMC7707640

Electronic International Standard Serial Number (EISSN)

  • 1934-6069

Digital Object Identifier (DOI)

  • 10.1016/j.chom.2020.11.012

Language

  • eng

Conference Location

  • United States