Evaluation of the Clinical Potential of Novel Rapid Cytokine Release Assays to Monitor Infection-, Vaccine-, and Hybrid-Induced Immune Responses to SARS-CoV-2, TBEV, HBV, and Other Viruses

Our group has developed rapid cytokine release assays for analysis of SARS-CoV-2-specific T cells.

In summary these assays entail the stimulation of whole blood with 15-mer peptides with 11-amino acid overlap derived from proteins from infectious agents for 48 hours, followed by the recovery of plasma. This plasma is then analyzed for released cytokines, e.g., IFN-g, IL-2, etc.

The 15-mer peptides used as stimuli in these assays thus are presented on MHC class I and II to activate peptide-specific CD8+ and CD4+ T cells, respectively.

Importantly, there is no apparent waning of some of these responses over time, as opposed to the rapid decline in antibodies, making them feasible to define if patients suffer from post-COVID-disease.

We have used these assays to monitor vaccine-, infection-, and hybrid-induced (i.e., the combined effect of vaccination and naturally acquired COVID-19) immune responses to SARS-CoV-2 in healthy participants and vulnerable populations, which has resulted in several publications.

The aims of this grant proposal are thus to:Continue monitoring of the durability of T- and B-cell responses to SARS-CoV-2 in these cohorts.Develop and evaluate similar assays for other viruses including Tick-borne encephalitis virus (TBEV) and hepatitis B virus (HBV), using our established research networks.Evaluate the potential commercialization of these rapid, potentially high-throughput cytokine release assays as diagnostic tools for infectious agents.