Dataset Information

Lack of evidence of significant homology of SARS-CoV-2 spike sequences to myocarditis-associated antigens.

ABSTRACT:

Background

COVID-19 mRNA vaccines have proven to be highly safe and effective. Myocarditis is an adverse event associated with mRNA vaccination, especially in young male subjects. These events are rare and, in the majority of cases, resolve quickly. As myocarditis can be driven by autoimmune responses, we wanted to determine if the SARS-CoV-2 spike protein antigen encoded in the mRNA COVID vaccines had potential cross-reactivity with auto-antigens previously associated with myocarditis.

Methods

We performed a sequence identity comparison between SARS-CoV-2 spike protein-derived peptides and myocarditis-associated antigens. We also performed a structural analysis of these antigens and the SARS-CoV-2 spike protein to identify potential discontinuous 3-D epitope similarities.

Findings

We found no significant enrichment in the frequency of spike-derived peptides similar to myocarditis-associated antigens as compared to several controls.

Interpretation

Our results do not support the notion that increased occurrence of myocarditis after SARS-CoV-2-spike vaccination is mediated by a cross-reactive adaptive immune response.

SUBMITTER: Marrama D

PROVIDER: S-EPMC8733122 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Publications

Lack of evidence of significant homology of SARS-CoV-2 spike sequences to myocarditis-associated antigens.

Marrama Daniel D Mahita Jarjapu J Sette Alessandro A Peters Bjoern B

EBioMedicine 20220106

<h4>Background</h4>COVID-19 mRNA vaccines have proven to be highly safe and effective. Myocarditis is an adverse event associated with mRNA vaccination, especially in young male subjects. These events are rare and, in the majority of cases, resolve quickly. As myocarditis can be driven by autoimmune responses, we wanted to determine if the SARS-CoV-2 spike protein antigen encoded in the mRNA COVID vaccines had potential cross-reactivity with auto-antigens previously associated with myocarditis.< ...[more]

PMID: 34998242

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Project description:The emergence of vaccine-evading SARS-CoV-2 variants urges the need for vaccines that elicit broadly neutralizing antibodies (bnAbs). Here, we assess covalently circularized nanodiscs decorated with recombinant SARS-CoV-2 spike glycoproteins from several variants for eliciting bnAbs with vaccination. Cobalt porphyrin-phospholipid (CoPoP) was incorporated into the nanodisc to allow for anchoring and functional orientation of spike trimers on the nanodisc surface through their His-tag. Monophosphoryl-lipid (MPLA) and QS-21 were incorporated as immunostimulatory adjuvants to enhance vaccine responses. Following optimization of nanodisc assembly, spike proteins were effectively displayed on the surface of the nanodiscs and maintained their conformational capacity for binding with human angiotensin-converting enzyme 2 (hACE2) as verified using electron microscopy and slot blot assay, respectively. Six different formulations were prepared where they contained mono antigens; four from the year 2020 (WT, Beta, Lambda, and Delta) and two from the year 2021 (Omicron BA.1 and BA.2). Additionally, we prepared a mosaic nanodisc displaying the four spike proteins from year 2020. Intramuscular vaccination of CD-1 female mice with the mosaic nanodisc induced antibody responses that not only neutralized matched pseudo-typed viruses, but also neutralized mismatched pseudo-typed viruses corresponding to later variants from year 2021 (Omicron BA.1 and BA.2). Interestingly, sera from mosaic-immunized mice did not effectively inhibit Omicron spike binding to human ACE-2, suggesting that some of the elicited antibodies were directed towards conserved neutralizing epitopes outside the receptor binding domain. Our results show that mosaic nanodisc vaccine displaying spike proteins from 2020 can elicit broadly neutralizing antibodies that can neutralize mismatched viruses from a following year, thus decreasing immune evasion of new emerging variants and enhancing healthcare preparedness.

Dataset Information

Lack of evidence of significant homology of SARS-CoV-2 spike sequences to myocarditis-associated antigens.

Background

Methods

Findings

Interpretation

Publications

Lack of evidence of significant homology of SARS-CoV-2 spike sequences to myocarditis-associated antigens.

Similar Datasets

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