Immunogenic Amino Acid Motifs and Linear Epitopes of COVID-19 mRNA Vaccines

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.

Changes Over Time in COVID-19 Incidence, Vaccinations, Serum Spike IgG, and Viral Neutralizing Potential Among Individuals From a North American Gaming Venue

“…Potent vaccine responses among individuals with prior COVID-19 (significantly higher on average than vaccinated SARS-CoV-2–naive individuals) have been a consistent finding in our laboratory and published reports 24,25 . Such findings follow classical immunologic dogma that “recalls” responses are faster and amplified versus primary responses 26–28 .…”

“…Potent vaccine responses among individuals with prior COVID-19 (significantly higher on average than vaccinated SARS-CoV-2-naive individuals) have been a consistent finding in our laboratory and published reports. 24,25 Such findings follow classical immunologic dogma that "recalls" responses are faster and amplified versus primary responses. [26][27][28] Together, the data highlight the potential that exists for "boosting" adaptive SARS-CoV-2 immunity, particularly for those without prior COVID-19, as well as those with prior COVID-19.…”