Immunogenic amino acid motifs and linear epitopes of COVID-19 mRNA vaccines

Adam V. Wisnewski, Carrie A. Redlich, Jian Liu, Kathy Kamath, Queenie Ann Abad, Richard F. Smith, Louis Fazen, Romero Santiago, Julian Campillo Luna, Brian Martinez, Elizabeth Baum-Jones, Rebecca Waitz, Winston A. Haynes, John C. Shon

Research output: Contribution to journalArticlepeer-review

Abstract

Reverse vaccinology is an evolving approach for improving vaccine effectiveness and minimizing adverse responses by limiting immunizations to critical epitopes. Towards this goal, we sought to identify immunogenic amino acid motifs and linear epitopes of the SARS-CoV-2 spike protein that elicit IgG in COVID-19 mRNA vaccine recipients. Paired pre/post vaccination samples from N = 20 healthy adults, and post-vaccine samples from an additional N = 13 individuals were used to immunoprecipitate IgG targets expressed by a bacterial display random peptide library, and preferentially recognized peptides were mapped to the spike primary sequence. The data identify several distinct amino acid motifs recognized by vaccine-induced IgG, a subset of those targeted by IgG from natural infection, which may mimic 3-dimensional conformation (mimotopes). Dominant linear epitopes were identified in the C-terminal domains of the S1 and S2 subunits (aa 558–569, 627–638, and 1148–1159) which have been previously associated with SARS-CoV-2 neutralization in vitro and demonstrate identity to bat coronavirus and SARS-CoV, but limited homology to non-pathogenic human coronavirus. The identified COVID-19 mRNA vaccine epitopes should be considered in the context of variants, immune escape and vaccine and therapy design moving forward.

Original languageEnglish (US)
Article numbere0252849
JournalPloS one
Volume16
Issue number9 September
DOIs
StatePublished - Sep 2021
Externally publishedYes

ASJC Scopus subject areas

  • General

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