D614G Spike Mutation Increases SARS CoV-2 Susceptibility to Neutralization

Cell Host Microbe. 2021 Jan 13;29(1):23-31.e4. doi: 10.1016/j.chom.2020.11.012. Epub 2020 Dec 1.


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.

Keywords: COVID-19; D614G; LNP; SARS-CoV-2; Spike; electron micrograph; mRNA; neutralization; nucleoside-modified; vaccine.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Antibodies, Monoclonal / immunology
  • Binding Sites
  • COVID-19 / immunology
  • COVID-19 / therapy*
  • COVID-19 Serotherapy
  • COVID-19 Vaccines / immunology
  • Female
  • HEK293 Cells
  • Humans
  • Immunization, Passive / methods
  • Macaca mulatta
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Middle Aged
  • Mutation*
  • Neutralization Tests
  • SARS-CoV-2 / genetics*
  • SARS-CoV-2 / pathogenicity
  • Spike Glycoprotein, Coronavirus / chemistry
  • Spike Glycoprotein, Coronavirus / genetics*
  • Spike Glycoprotein, Coronavirus / immunology*
  • Young Adult


  • Antibodies, Monoclonal
  • COVID-19 Vaccines
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2