Towards a protein-based diagnostic that accurately measures anyone's ability to respond to COVID-19

Overview

Background. The protective effects of coronavirus vaccines rely on their ability to mount a long-term immune response; the initial response that results in immune memory relies on T cells and their ability to recognize virus specific epitopes, secrete cytokines, express cell surface molecules, and proliferate. However, this memory, measured by antibody response, often decreases over time. Furthermore, although the SARS-CoV-2 spike protein is researchers’ primary target, more conserved non-structural proteins (NSPs) of SARS-CoV-2 can be better targets if sufficiently immunogenic. Consequently, our hypothesis was to assess T-cell responses to the spike protein and non-structural proteins of SARS-CoV-2 in donors with different immunization and infection histories. Methods. To probe for T-cell response to SARS-CoV-2, 12-mer immunodominant peptide epitopes from the virus’ NSPs were designed using major histocompatibility complex binding prediction tools from the Immune Epitope Database. These viral epitopes from both spike protein and NSPs were then cultured individually with human peripheral blood mononuclear cells (PBMCs) of donors vaccinated with either the Moderna or Pfizer mRNA vaccines. The controls were donors who had never been exposed to coronavirus. Next, the T-cell cytokines secreted following culture were assessed by a multiplexed proteomics platform to measure the strength of the donors’ functional response. Results. Distinct T-cell cytokine profiles were observed in donors based on their immunization histories. Data from three specific cytokines—interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-a) and interferon-gamma (IFN-Y)—demonstrated how donors’ response differed in individuals with different immunization and SARS-CoV-2 infection history. Fully-vaccinated donors showed a robust T-cell response, especially to the spike protein, while previously infected donors with no vaccination history responded greater to NSP epitopes. Longitudinal studies in fully vaccinated donors over a period of 6 months showed a reduced response to both the spike protein and NSPs. After donors received the second dose of the vaccine, the assay responses revealed that their immunity was boosted since the first dose. Conclusion. We have demonstrated that immunodominant peptides from both SARS-CoV-2 NSPs and spike protein can induce robust antigen-specific T-cell cytokine responses. This assay could be utilized to measure immune memory in donors vaccinated with various SARS-CoV-2 vaccines, especially as new data is generated with unique donors.

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Awards (1)

• AJAS Fellows Badge

Competition history

• AJAS 2022 Microbiology

Resources

• My Story AJAS.pdf ↗

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