High resolution linear epitope mapping of the receptor binding domain of SARS-CoV-2 spike protein in COVID-19 mRNA vaccine recipients

Abstract

The prompt rollout of the coronavirus disease (COVID-19) messenger RNA (mRNA) vaccine facilitated population immunity, which shall become more dominant than natural infection-induced immunity. At the beginning of the vaccine era, the initial epitope profile in naive individuals will be the first step to build an optimal host defense system towards vaccine-based population immunity. In this study, the high-resolution linear epitope profiles between Pfizer-BioNTech COVID-19 mRNA vaccine recipients and COVID-19 patients were delineated by using microarrays mapped with overlapping peptides of the receptor binding domain (RBD) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. The vaccine-induced antibodies targeting RBD had broader distribution across the RBD than that induced by the natural infection. The relatively lower neutralizing antibody titers observed in vaccine-induced sera could attribute to less efficient epitope selection and maturation of the vaccine-induced humoral immunity compared to the infection-induced. Furthermore, additional mutation panel assays showed that the vaccine-induced rich epitope variety targeting the RBD may aid antibodies to escape rapid viral evolution, which could grant an advantage to the vaccine immunity.

Immunogenicity and safety of COVID-19 vaccine in lung cancer patients receiving anticancer treatment: A prospective multicenter cohort study

“…This discrepancies in results between the two assays might be because of the different methods used to identify the antibodies. 32 First, the repertoire of the antibodies might affects the titers measured in each immunoassay 33 . Second, Elecsys uses the double-antigen sandwich method, whereas Architect uses a chemiluminescent microparicle immunoassay 15, 16 The Elecsys platform based on the double-antigen sandwich method has shown tendency towards detecting antibodies with higher avidity.…”

Antibody avidity maturation favors SARS-CoV-2 convalescents over vaccinated individuals granting breadth in neutralizability and tolerance against variants

“…Additionally, the urea-resistant fraction of the antibody titer was predictive of neutralizability only following the second dose of the vaccine. In contrast to the limited variety of epitopes recurrently targeted across convalescent individuals [30], the vaccine-elicited immune response is mapped to a broadened epitope landscape [31,32]. During the initial response to the SARS-CoV-2 vaccine, the majority of urea-resistant signals obtained from our avidity ELISA were possibly from a widely dispersed, non-neutralizing antibody repertoire that still dominated the week-3 vaccinees’ sera.…”

Antibody isotype epitope mapping of SARS‐CoV‐2 Spike RBD protein: Targets for COVID‐19 symptomatology and disease control

“…Recent results using RBD epitope mapping with antibodies from COVID-19 patients and healthy individuals immunized with the Pfizer-BioNTech COVID-19 mRNA vaccine (https://www.cdc.gov/coronavirus/2019ncov/vaccines/different-vaccines/Pfizer-BioNTech.html) [40] identified epitopes recognized by both cohorts (e.g., 449-YNYLYRLFRKSNLKP-463) or by vaccinated individuals only (e.g., 363-ADYSVLYNSASFSTFKCY-380 and 332-ITNLCPFGEV-341) and present in regions identified in our study (Table 1).…”

“…Considering the results of the RBD epitope mapping reported here and previous results with tick vaccine antigens [43,44], we proposed the candidate SARS-CoV-2 protective chimeric antigen MKLLE-487-NCYFPLQSYGFQPTNGVG-504-GGGGS-446-GGNYNYLYRLFRKSNLKPFERD-467. The chimeric antigen contains epitopes identified before as reactive in Pfizer-BioNTech vaccinated individuals (449-YNYLYRLFRKSNLKP-463; [40]) and in the synthetic peptide RBD 446-480 shown to induce cross-reactive humoral neutralizing and cellular CD4 and CD8 responses in preclinical trials in mice (RBD 446-467; [45]).…”