SAFETY AND SPECIFIC ACTIVITY OF THE RECOMBINANT SARS-COV-2 (CORONADERM-PS) ALLERGEN BASED ON PHASE I-II CLINICAL TRIAL RESULTS

Abstract

Abstract The evaluation of cellular immunity to SARS-CoV-2 is a critical tool for assessing vaccination efficacy and development of post-infectious immunity. According to available studies, virus-specific T cells persist longer than antigen-specific antibodies and play a pivotal role in the effective virus elimination from human body. Current methodologies for assessing virus-specific T cells are mostly based on flow cytometry, which require specialized laboratory equipment and highly trained personnel. An alternative approach involves a skin test conducted to assess delayed-type hypersensitivity (DTH) reactions. For this, there has been developed the "CoronaDerm-PS" substance, a sterile isotonic solution for intradermal administration, containing a recombinant hybrid protein that incorporates regions of SARS-CoV-2 structural proteins S, M, N, and E, produced by a genetically modified E. coli BL21 strain cell culture. Following preclinical studies that demonstrated the safety of the above-noted medication, Phase I and Phase II clinical trials were initiated to evaluate safety and specific activity of "CoronaDerm-PS" in apparently healthy volunteers with SARS-CoV-2 post-vaccination and post-infection immunity. In Phase I clinical trial with COVID-19 unexposed or vaccinated volunteers, the data were obtained demonstrating the safety and good tolerability of the medication, thus enabling the progression to Phase II. The Phase II results provided additional evidence on the preparation’s safety in individuals with SARS-CoV-2 post-vaccination and post-infection immunity, as assessed by clinical and laboratory data. No serious adverse events were observed during the study, and in 93.5% cases, adverse events required no therapeutic or diagnostic intervention. To assess the specific activity of the preparation, the skin test data were compared with the IFNγ production stimulation index for CD4+ T lymphocytes assessed by flow cytometry. The ROC analysis revealed sensitivity magnitude ranging from 76.6% to 84%, and specificity level ranging from 80% to 87.5%. Based on ROC analysis results, "CoronaDerm-PS" can be an informative diagnostic tool (AUC = 0.795), demonstrating high sensitivity (79.8%) and specificity (80.8%), with consistent results across different volunteer cohorts. Analyzing the collected data suggests that "CoronaDerm-PS" is a robust alternative to laboratory methods for evaluating SARS-CoV-2-specific T-cell immunity, with high sensitivity and specificity, suitable for large-scale screening.