The SARS-CoV-2 spike residues 616/644 and 1138/1169 delineate two antibody epitopes in COVID-19 mRNA COMIRNATY vaccine (Pfizer/BioNTech)

Abstract

The newly identified coronavirus SARS-CoV-2 is responsible for the worldwide pandemic COVID-19. Considerable efforts have been devoted for the development of effective vaccine strategies against COVID-19. The SARS-CoV-2 spike protein has been identified as the major antigen candidate for the development of COVID-19 vaccines. The Pfizer-BioNTech COVID-19 vaccine comirnaty is a lipid nanoparticle-encapsulated mRNA encoding a full-length and prefusion-stabilized SARS-CoV-2 spike protein. In the present study, synthetic peptide-based ELISA assays were performed to identify linear B-cell epitopes into the spike protein that contribute to elicitation of antibody response in comirnaty-vaccinated individuals. The synthetic S2P6 peptide containing the spike residues 1138/1169 and to a lesser extent, the synthetic S1P4 peptide containing the spike residues 616/644 were recognized by the immune sera from comirnaty vaccine recipients but not COVID-19 recovered patients. We assume that the synthetic S2P6 peptide and to a lesser extent the synthetic S1P4 peptide, could be of interest to measure the dynamic of antibody response to COVID-19 mRNA vaccines. The S2P6 peptide has been identified as immunogenic in adult BALB/c mice that received protein-peptide conjugates in a prime-boost schedule. This raises the question on the role of the B-cell epitope peptide containing the SARS-CoV-2 spike residues 1138/1169 in protective efficacy of the Pfizer-BioNTech COVID-19 vaccine comirnaty.

Potential Autoimmunity Resulting from Molecular Mimicry between SARS-CoV-2 Spike and Human Proteins

“…In COVID-19, stronger antibody responses to the epitope containing the ELDKY motif have been recorded for severe (requiring hospitalization) vs. moderate cases, while fatal cases had a weaker response than surviving cases [ 16 ]. A synthetic epitope containing the ELDKY motif has also been shown to elicit antibody production following COVID-19 immunization [ 70 ]. Together with the 3D mimics identified here, these results suggest interesting possibilities for the ELDKY motif from the perspective of both protective immunity and an autoimmune response.…”

The Gold Nanoparticles-Functionalized with the Synthetic PADRE^S2P6 Peptide Can Be Useful for SARS-CoV-2 Detection

“…We recently reported that peptide-reactive antibodies were detected in mice immunized with the synthetic S2P6 peptide, and to a lesser extent the synthetic S1P4 peptide, coupled to protein carrier keyhole limpet hemocyanin (KLH) [4]. The present study aimed at investigating the ability of AuNPs to bioconjugate with two SARS-CoV-2 spike epitope peptides, as well as to trigger an humoral response against the AuNP-peptide conjugates in a mouse model.…”

“…Nanomedicines have demonstrated their usefulness in vaccine platforms and nanoparticle-encapsulated COVID-19 mRNA vaccines marketed as Comirnaty (BNT162 vaccine under license from Pfizer/BioNTech) and Spikevax (under license from Moderna) have greatly contributed to the fight against SARS-CoV-2, the etiologic agent of COVID-19. We recently reported that individuals who had received COVID-19 mRNA Comirnaty vaccine developed antibodies recognizing two linear B-cell epitopes, namely S1P4 and S2P6, located in the spike protein of SARS-CoV-2 [4]. There was a lack of reactivity of S1P4 and S2P6 antibody epitopes with immune sera from COVID-19 recovered patients suggesting that their immune recognition would be an antigenic property of recombinant spike protein expressed by Comirnaty vaccine [4].…”

“…We recently reported that individuals who had received COVID-19 mRNA Comirnaty vaccine developed antibodies recognizing two linear B-cell epitopes, namely S1P4 and S2P6, located in the spike protein of SARS-CoV-2 [4]. There was a lack of reactivity of S1P4 and S2P6 antibody epitopes with immune sera from COVID-19 recovered patients suggesting that their immune recognition would be an antigenic property of recombinant spike protein expressed by Comirnaty vaccine [4]. SARS-CoV-2 spike protein is structurally divided into S1 and S2 subunits [2].…”

“…S1P4 antibody epitope (residues S-616 to S-644) localizes to the C-terminal region of S1 subunit whereas S2P6 antibody epitope (residues S-1138 to S-1169) is found downstream of the transmembrane domain of S2 subunit. So far, the two antibody epitope sequences are strictly conserved among recent SARS-CoV-2 Variants of Concern (VOC) including Omicron [4].…”