Immunogenic amino acid motifs and linear epitopes of COVID-19 mRNA vaccines
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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.
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SciScore for 10.1101/2021.05.25.21257427: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: The investigation was approved by the Yale University Institutional Review Board (IRB) and all study subjects provided written informed consent before participating in the study.
Consent: The investigation was approved by the Yale University Institutional Review Board (IRB) and all study subjects provided written informed consent before participating in the study.Sex as a biological variable not detected. Randomization Briefly, serum was incubated with a fully random 12-mer bacterial display peptide library (1×1010 diversity, 10-fold oversampled) at a 1:25 dilution in a 96-well, deep well plate format. Blinding not detected. Power Analysis not detected. Table 2: Resources
Antibodies Sentences Reso… SciScore for 10.1101/2021.05.25.21257427: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: The investigation was approved by the Yale University Institutional Review Board (IRB) and all study subjects provided written informed consent before participating in the study.
Consent: The investigation was approved by the Yale University Institutional Review Board (IRB) and all study subjects provided written informed consent before participating in the study.Sex as a biological variable not detected. Randomization Briefly, serum was incubated with a fully random 12-mer bacterial display peptide library (1×1010 diversity, 10-fold oversampled) at a 1:25 dilution in a 96-well, deep well plate format. Blinding not detected. Power Analysis not detected. Table 2: Resources
Antibodies Sentences Resources Plates were washed three times with PBS-T (PBS with 0.1% Tween-20) and incubated with 50 μL of HRP anti-Human IgG Antibody (Pharmingen, 1:2,000) for 1 h at RT. anti-Human IgGsuggested: NoneSoftware and Algorithms Sentences Resources Blood was obtained by venipuncture in a serum separator tube (BD Vacutainer®, Franklin Lakes, NJ) and the serum fraction was separated following centrifugation and stored at -80°C. BD Vacutainer®suggested: NoneStatistical analysis: GraphPad Prism (v8) and Microsoft Excel for Windows 10 (v16.0.13001.20254) were used for statistical analyses. GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)Microsoft Excelsuggested: (Microsoft Excel, RRID:SCR_016137)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:The findings are consistent with prior reports that did not detect spike RBD linear epitopes and may be due to multiple reasons including limitations in sensitivity and frequency/sample size, as well as the RBD’s complex secondary structure, which is thought to form immunogenic 3-D conformations, or non-continuous epitopes (11, 13, 17, 26). RBD specific antibodies are a minor proportion of total anti-spike IgG and linear RBD epitopes are not prominent IgG epitopes in natural SARS-CoV-2 infection (12, 13, 27). Nonetheless, the RBD is an important target of neutralizing antibodies that develop in vivo during natural infection (28), and possibly a driver for the evolution of mutations given its critical role in the virus life cycle (29, 30). Many of the SARS-CoV-2 variants that have evolved to date contain mutations that affect the RBD and result in decreased neutralization by RBD-specific antibodies (31), but not mAbs that bind outside the receptor-binding motif (32, 33). In this context dominant linear neutralizing epitopes may provide an increased role in immunity and compensate for loss of neutralization activity due to decreased IgG recognition of variant RBDs, and perhaps contribute to current mRNA vaccine efficacy in populations with high prevalence of B.1.1.7 and B.1.351 variants (34). Mutations that result in escape from dominant linear epitopes outside the RBD might also adversely affect host immunity and vaccine efficacy, particularly if compounded by RBD escape varia...
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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