The SARS-CoV-2 Delta variant induces an antibody response largely focused on class 1 and 2 antibody epitopes

PLoS Pathog. 2022 Jun 29;18(6):e1010592. doi: 10.1371/journal.ppat.1010592. eCollection 2022 Jun.

Abstract

Exposure histories to SARS-CoV-2 variants and vaccinations will shape the specificity of antibody responses. To understand the specificity of Delta-elicited antibody immunity, we characterize the polyclonal antibody response elicited by primary or mRNA vaccine-breakthrough Delta infections. Both types of infection elicit a neutralizing antibody response focused heavily on the receptor-binding domain (RBD). We use deep mutational scanning to show that mutations to the RBD's class 1 and class 2 epitopes, including sites 417, 478, and 484-486 often reduce binding of these Delta-elicited antibodies. The anti-Delta antibody response is more similar to that elicited by early 2020 viruses than the Beta variant, with mutations to the class 1 and 2, but not class 3 epitopes, having the largest effects on polyclonal antibody binding. In addition, mutations to the class 1 epitope (e.g., K417N) tend to have larger effects on antibody binding and neutralization in the Delta spike than in the D614G spike, both for vaccine- and Delta-infection-elicited antibodies. These results help elucidate how the antigenic impacts of SARS-CoV-2 mutations depend on exposure history.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Antibody Formation
  • COVID-19*
  • Epitopes
  • Humans
  • Neutralization Tests
  • SARS-CoV-2* / genetics
  • Spike Glycoprotein, Coronavirus / metabolism
  • Vaccines, Synthetic
  • mRNA Vaccines

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Epitopes
  • Spike Glycoprotein, Coronavirus
  • Vaccines, Synthetic
  • mRNA Vaccines
  • spike protein, SARS-CoV-2

Supplementary concepts

  • SARS-CoV-2 variants