Safety and specific activity of the recombinant SARS-CoV-2 allergen (“CoronaDerm-PS”) based on phase I–II clinical trial results
- Authors: Savin T.V.1,2, Milichkina A.M.1, Krasnov A.A.1, Kuznetsova R.N.3,2, Shchederkina E.E.1, Svarval A.V.1, Sharova A.А.1, Reingardt D.E.1, Ostankova Y.V.1, Gubanova A.V.1, Petrova O.A.1,2, Zhimbaeva O.B.1, Razumovskaya A.P.1, Drozd I.V.1, Rubinstein A.А.4, Trulev A.S.4, Kudryavtsev I.V.2,4, Riabchenkova A.A.5, Chirak E.L.5, Chirak E.R.5, Saenko A.I.5, Kopat V.V.5, Dukhovlinov I.V.5, Simbirtsev A.S.1,2, Totolian A.A.1,2
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Affiliations:
- St. Petersburg Pasteur Institute
- Pavlov First St. Petersburg State Medical University
- St. Petersburg Pasteur Institute, St. Petersburg
- Institute of Experimental Medicine
- LLC “ATG Service-Gene”
- Issue: Vol 14, No 5 (2024)
- Pages: 900-916
- Section: ORIGINAL ARTICLES
- URL: https://journal-vniispk.ru/2220-7619/article/view/284794
- DOI: https://doi.org/10.15789/2220-7619-SAS-17790
- ID: 284794
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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.
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##article.viewOnOriginalSite##About the authors
Tikhon V. Savin
St. Petersburg Pasteur Institute; Pavlov First St. Petersburg State Medical University
Author for correspondence.
Email: savin@pasteurorg.ru
Allergologist-Immunologist, Senior Laboratory Assistant, Department of Immunology
Russian Federation, St. Petersburg; St. PetersburgA. M. Milichkina
St. Petersburg Pasteur Institute
Email: savin@pasteurorg.ru
PhD (Medicine), Head Physician of the Medical Center
Russian Federation, Saint PetersburgA. A. Krasnov
St. Petersburg Pasteur Institute
Email: savin@pasteurorg.ru
DSc (Medicine), Senior Researcher, Department of Biomedical Statistics
Russian Federation, St. PetersburgR. N. Kuznetsova
St. Petersburg Pasteur Institute, St. Petersburg; Pavlov First St. Petersburg State Medical University
Email: savin@pasteurorg.ru
PhD (Medicine), allergologist-immunologist
Associate Professor, Department of Immunology
Russian Federation, St. Petersburg; St. PetersburgE. E. Shchederkina
St. Petersburg Pasteur Institute
Email: savin@pasteurorg.ru
PhD (Medicine), Doctor of Clinical Laboratory Diagnostics, Laboratory of Molecular Genetic Diagnostics
Russian Federation, St. PetersburgA. V. Svarval
St. Petersburg Pasteur Institute
Email: savin@pasteurorg.ru
PhD (Medicine), Senior Researcher, Head of the Pathogens Identification Laboratory
Russian Federation, St. PetersburgA. А. Sharova
St. Petersburg Pasteur Institute
Email: savin@pasteurorg.ru
Junior Researcher, Laboratory of Molecular Genetic Monitoring
Russian Federation, St. PetersburgD. E. Reingardt
St. Petersburg Pasteur Institute
Email: savin@pasteurorg.ru
Doctor of Clinical Laboratory Diagnostic, Department of Diagnostics of HIV Infection and AIDS-related Diseases
Russian Federation, St. PetersburgYu. V. Ostankova
St. Petersburg Pasteur Institute
Email: savin@pasteurorg.ru
PhD (Biology), Head of the Laboratory of immunology and Virology HIV Infection, Senior Researcher of the Laboratory of Molecular Immunology
Russian Federation, St. PetersburgA. V. Gubanova
St. Petersburg Pasteur Institute
Email: savin@pasteurorg.ru
Doctor of Clinical Laboratory Diagnostics, Central Clinical Diagnostic Laboratory of the Medical Center
Russian Federation, Saint PetersburgO. A. Petrova
St. Petersburg Pasteur Institute; Pavlov First St. Petersburg State Medical University
Email: savin@pasteurorg.ru
Doctor of Clinical Laboratory Diagnostics
Russian Federation, Saint Petersburg; Saint PetersburgO. B. Zhimbaeva
St. Petersburg Pasteur Institute
Email: savin@pasteurorg.ru
Physician, Central Clinical Diagnostic Laboratory of the Medical Center
Russian Federation, Saint PetersburgA. P. Razumovskaya
St. Petersburg Pasteur Institute
Email: savin@pasteurorg.ru
Doctor of Clinical Laboratory Diagnostics, Central Clinical Diagnostic Laboratory of the Medical Center
Russian Federation, Saint PetersburgI. V. Drozd
St. Petersburg Pasteur Institute
Email: savin@pasteurorg.ru
PhD (Biology), Head of the Central Clinical Diagnostic Laboratory
Russian Federation, Saint PetersburgA. А. Rubinstein
Institute of Experimental Medicine
Email: savin@pasteurorg.ru
Junior Researcher, Cell Immunology Laboratory, Department of Immunology
Russian Federation, St. PetersburgA. S. Trulev
Institute of Experimental Medicine
Email: savin@pasteurorg.ru
PhD (Biology), Researcher, Department of Immunology
Russian Federation, St. PetersburgI. V. Kudryavtsev
Pavlov First St. Petersburg State Medical University; Institute of Experimental Medicine
Email: savin@pasteurorg.ru
PhD (Biology), Assistant Professor, Department of Immunology, Head of the Cell Immunology Laboratory, Department of Immunology
Russian Federation, Saint Petersburg; Saint PetersburgA. A. Riabchenkova
LLC “ATG Service-Gene”
Email: savin@pasteurorg.ru
Researcher
Russian Federation, St. PetersburgE. L. Chirak
LLC “ATG Service-Gene”
Email: savin@pasteurorg.ru
Researcher
Russian Federation, St. PetersburgE. R. Chirak
LLC “ATG Service-Gene”
Email: savin@pasteurorg.ru
Researcher
Russian Federation, St. PetersburgA. I. Saenko
LLC “ATG Service-Gene”
Email: savin@pasteurorg.ru
Chief Process Engineer
Russian Federation, St. PetersburgV. V. Kopat
LLC “ATG Service-Gene”
Email: savin@pasteurorg.ru
Development Director
Russian Federation, St. PetersburgI. V. Dukhovlinov
LLC “ATG Service-Gene”
Email: savin@pasteurorg.ru
PhD (Biology), Director of Science
Russian Federation, St. PetersburgA. S. Simbirtsev
St. Petersburg Pasteur Institute; Pavlov First St. Petersburg State Medical University
Email: savin@pasteurorg.ru
RAS Corresponding Member, DSc (Medicine), Professor, Head of the Laboratory of Medical Biotechnology, Professor of the Department of Immunology
Russian Federation, St. Petersburg; St. PetersburgA. A. Totolian
St. Petersburg Pasteur Institute; Pavlov First St. Petersburg State Medical University
Email: savin@pasteurorg.ru
RAS Full Member, DSc (Medicine), Professor, Head of the Laboratory of Molecular Immunology, Director, Head of the Department of Immunology
Russian Federation, St. Petersburg; St. PetersburgReferences
- Копать В.В., Рябченкова А.А., Чирак Е.Л., Чирак Е.Р., Саенко А.И., Колмаков Н.Н., Симбирцев А.С., Духовлинов И.В., Тотолян А.А. Разработка структуры и штамма-продуцента E. coli для антигена, содержащего последовательности белков N, S, M, E коронавируса SARS-CоV-2 // Инфекция и иммунитет. 2023. Т. 13, № 5. C. 653–662. [Kopat V.V., Riabchenkova A.A., Chirak E.L., Chirak E.R., Saenko A.I., Kolmakov N.N., Simbirtsev A.S., Dukhovlinov I.V., Totolian A.A. Designing structure and E. coli strain-producer bearing SARS-CoV-2 N, S, M, E proteinrelated sequence antigen. Infektsiya i immunitet = Russian Journal of Infection and Immunity, 2023, vol. 13, no. 4, pp. 653–662. (In Russ.)] doi: 10.15789/2220-7619-DSA-15624
- Копать В.В., Рябченкова А.А., Чирак Е.Л., Чирак Е.Р., Саенко А.И., Кудрявцев И.В., Трулев А.С., Савин Т.В., Зуева Е.В., Симбирцев А.С., Тотолян А.А., Духовлинов И.В. Разработка технологии очистки, биохимическая и иммунологическая характеристика рекомбинантного химерного антигена для оценки Т-клеточного иммунитета против коронавирусной инфекции // Медицинская иммунология. 2024. Т. 26, № 3. С. 591–606. [Kopat V.V., Riabchenkova A.A., Chirak E.L., Chirak E.R., Saenko A.I., Kudryavtsev I.V., Trulioff A.S., Savin T.V., Zueva E.V., Simbirtsev A.S., Totolian A.A., Dukhovlinov I.V. Purification technology design, biochemical and immunological characteristics of the recombinant chimeric antigen for evaluation of T cell immunity against coronavirus infection. Meditsinskaya immunologiya = Medical Immunology (Russia), 2024, vol. 26, no. 3, pp. 591–606. (In Russ.)] doi: 10.15789/1563-0625-PTD-2942
- Савин Т.В., Копать В.В., Рябченкова А.А., Чирак Е.Л., Чирак Е.Р., Саенко А.И., Духовлинов И.В., Сысоева Г.М., Гамалей С.Г., Шимина Г.Г., Таранов О.С., Даниленко Е.Д., Симбирцев А.С., Тотолян А.А. Экспериментальное исследование специфической иммунологической активности и безопасности препарата «КоронаДерм-PS» для оценки клеточного иммунитета против коронавируса SARS-CoV-2 // Инфекция и иммунитет. 2024. Т. 14, № 2. C. 238–250. [Savin T.V., Kopat V.V., Riabchenkova A.A., Chirak E.L., Chirak E.R., Saenko A.I., Dukhovlinov I.V., Sysoeva G.M., Gamaley S.G., Shimina G.G., Taranov O.S., Danilenko E.D., Simbirtsev A.S., Totolian A.A. Experimentally investigated “CoronaDerm-PS”-driven SARS-CoV-2-specific cellular immunity and safety. Infektsiya i immunitet = Russian Journal of Infection and Immunity, 2024, vol. 14, no. 2, pp. 238–250. (In Russ.)] doi: 10.15789/2220-7619- ESO-17661
- Adamo S., Michler J., Zurbuchen Y., Cervia C., Taeschler P., Raeber M.E., Baghai Sain S., Nilsson J., Moor A.E., Boyman O. Signature of long-lived memory CD8+ T cells in acute SARS-CoV-2 infection. Nature, 2022, vol. 602, no. 7895, pp. 148–155. doi: 10.1038/s41586-021-04280-x
- Bertoletti A., Le Bert N., Tan A.T. SARS-CoV-2-specific T cells in the changing landscape of the COVID-19 pandemic. Immunity, 2022, vol. 55, no. 10, pp. 1764–1778. doi: 10.1016/j.immuni.2022.08.008
- Kudryavtsev I., Rubinstein A., Golovkin A., Kalinina O., Vasilyev K., Rudenko L., Isakova-Sivak I. Dysregulated immune responses in SARS-CoV-2-infected patients: a comprehensive overview. Viruses, 2022, vol. 14, no. 5: 1082. doi: 10.3390/v14051082
- Lin Y., Zhu J., Liu Z., Li C., Guo Y., Wang Y., Chen K. Kinetics of severe acute respiratory syndrome coronavirus 2 infection antibody responses. Front. Immunol., 2022, no. 13: 864278. doi: 10.3389/fimmu.2022.864278
- Mantoux Ch. Intradermo-réaction de la tuberculine. Compt. Rend. Acad. Sci., 1908, vol. 147, pp. 355–357.
- Matyushenko V., Isakova-Sivak I., Kudryavtsev I., Goshina A., Chistyakova A., Stepanova E., Prokopenko P., Sychev I., Rudenko L. Detection of IFNγ-Secreting CD4+ and CD8+ Memory T Cells in COVID-19 Convalescents after Stimulation of Peripheral Blood Mononuclear Cells with Live SARS-CoV-2. Viruses, 2021, vol. 13, no. 8: 1490. doi: 10.3390/v13081490
- Sekine T., Perez-Potti A., Rivera-Ballesteros O., Strålin K., Gorin J.B., Olsson A., Llewellyn-Lacey S., Kamal H., Bogdanovic G., Muschiol S., Wullimann D.J., Kammann T., Emgård J., Parrot T., Folkesson E.; Karolinska COVID-19 Study Group, Rooyackers O., Eriksson L.I., Henter J.I., Sönnerborg A., Allander T., Albert J., Nielsen M., Klingström J., Gredmark-Russ S., Björkström N.K., Sandberg J.K., Price D.A., Ljunggren H.G., Aleman S., Buggert M. Robust T Cell Immunity in Convalescent Individuals with Asymptomatic or Mild COVID-19. Cell, 2020, vol. 183, no. 1, pp. 158–168.e14. doi: 10.1016/j.cell.2020.08.017
- Shao W., Chen X., Zheng C., Liu H., Wang G., Zhang B., Li Z., Zhang W. Effectiveness of COVID-19 vaccines against SARS-CoV-2 variants of concern in real-world: a literature review and meta-analysis. Emerg. Microbes Infect., 2022, vol. 11, no. 1, pp. 2383–2392. doi: 10.1080/22221751.2022.2122582
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