To the content
4 . 2024
PDF (RUS)

T-cell sensitization dynamics after intranasal and intramuscular immunization with a two-component vector vaccine for the prevention of coronavirus infection based on Ad26 and Ad5

Abstract

Introduction. The mucosal route of immunization is the focus of investigators for many years and COVID-19 is not exception. One of the objective parameters for assessing immunological effectiveness is the study of T-cell sensitization in the blood of recovered COVID-19 patients or healthy volunteers received vaccine prophylaxis. T-cell immunity to SARS-CoV-2 assessment is important not only for risk stratification and identifying potentially protected populations with immunity acquired through infection, but also for determining the immunogenicity and potential effectiveness of vaccines under development. The results of an interim analysis of data obtained as part of a randomized, double-blind, multicenter phase III clinical trial of a two-component vaccine for the prevention of COVID-19 with intranasal and intramuscular routes of administration are presented.

Aim – to evaluate the T-cell response dynamics to various peptides of the SARS-CoV-2 against after intranasal and intramuscular immunization with a two-component vector vaccine to prevent the development of COVID-19.

Material and methods. A total of 137 healthy volunteers with a baseline anti-RBD IgG level not exceeding 100 BAU/ml received immunization by a two-component (Ad26 and Ad5 based) intranasal or intramuscular vaccine administered on day 1 and day 21. Immunogenicity assessment was based on T-cell response data using IGRA-ELISPOT technology on days 21 and 42 after administration of component I.

Results. The proportion of patients with T-cell sensitization to the SARS-CoV-2 significantly increased after intranasal (from the baseline level of 33.9 % to 55.93 % on day 42) and intramuscular (from the baseline level of 30.51 % to 61.02 % on day 42) immunization and was comparable between groups at all visits. There is a statistically significant increase in the number of SARS-CoV-2 spike (S) protein-specific T cells (total CD8+ and CD4+) and the absence of sensitization of these cells to the N, M, ORF3a and ORF7a proteins of the virus.

Conclusion. The immunogenic potential of a two-component vector vaccine (based on Ad26 and Ad5) with clonal activation of T cells to the spike (S) protein of the SARS-CoV-2 after intranasal or intramuscular administration has been shown.

Keywords: ELISPOT; SARS-CoV-2; COVID-19; T-lymphocytes; antibodies; vaccine; immunity

For citation: Zuev E.V., Markova O.A., Khamitov R.A. T-cell sensitization dynamics after intranasal and intramuscular immunization with a two-component vector vaccine for the prevention of coronavirus infection based on Ad26 and Ad5. Immunologiya. 2024; 45 (4): 456–64. DOI: https://doi.org/10.33029/1816-2134-2024-45-4-456-464 in Russian)

Funding. The study was supported by GENERIUM JSC.

Conflict of interests. The authors declare no conflict of interests.

Authors’ contribution. Concept and design of the study – Zuev E.V.; writing the text – Zuev E.V.; editing and approval of the final material of the article – Markova O.A., Hamitov R.A.; responsibility for the integrity of all parts of the article – Zuev E.V.

References

1. Spasennikov B.A. COVID-19: lessons of vaccination. Bulletin of Semashko National Research Institute of Public Health. 2021; 3: 116–25. DOI: https://doi.org/10.25742/NRIPH.2021.03.017 (in Russian)

2. Gudima G.O., Khaitov R.M., Kudlay D.A., Khaitov M.R. Molecular immunological aspects of diagnostics, prevention and treatment of coronavirus infection. Immunologiya. 2021; 42 (3): 198–210. DOI: https://doi.org/10.33029/0206-4952-2021-42-3-198-210 (in Russian)

3. Logunov D.Y., Dolzhikova I.V., Zubkova O.V., Tukhvatulin A.I., Shcheblyakov D.V., Dzharullaeva A.S., Grousova D.M., Erokhova A.S., Kovyrshina A.V., Botikov A.G., Izhaeva F.M., Popova O., Ozharovskaya T.A., Esmagambetov I.B., Favorskaya I.A., Zrelkin D.I., Voronina D.V., Shcherbinin D.N., Semikhin A.S., Simakova Y.V., Tokarskaya E.A., Lubenets N.L., Egorova D.A., Shmarov M.M., Nikitenko N.A., Morozova L.F., Smolyarchuk E.A., Kryukov E.V., Babira V.F., Borisevich S.V., Naroditsky B.S., Gintsburg A.L. Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomised phase 1/2 studies from Russia. Lancet. 2020; 396 (10255): 887–97. DOI: https://doi.org/10.1016/S0140-6736(20)31866-3

4. Morozov A.N., Yakhin I.R., Stratonova N.V., Kutskir M.V., Poteryaev D.A., Khamitov R.A. An experience of scaling and intensifying the industrial production of the Gam-COVID-Vac vector adenovirus vaccine in the limiting conditions of the pandemic. Biological Products. Prevention, Diagnosis, Treatment. 2022; 22 (4): 382–91. DOI: https://doi.org/10.1016/S0140-6736(20)31866-3 (in Russian)

5. Andreev I.V., Nechay K.O., Andreev A.I., Zubaryova A.P., Esaulova D.R., Alenova A.M., Nikolaeva I.A., Chernyavskaya O.P., Lomonosov K.S., Shulzhenko A.E., Kurbacheva O.M., Latysheva E.A., Shartanova N.V., Nazarova E.V., Romanova L.V., Cherchenko N.G., Smirnov V.V., Averkov O.V., Martynov A.I., Vechorko V.I., Gudima G.O., Kudlay D.A., Khaitov M.R., Khaitov R.M. Post-vaccination and post-infection humoral immune response to the SARS-CoV-2 infection. Immunologiya. 2022; 43 (1): 18–32. DOI: https://doi.org/10.33029/0206-4952-2022-43-1-18-32 (in Russian)

6. Andreev A.I., Andreev I.V., Nechay K.O., Esaulova D.R., Baklakova O.S., Vechorko V.I., Shilovskiy I.P., Kofiadi I.A, Gudima G.O., Martynov A.I., Smirnov V.V., Kudlay D.A., Khaitov M.R. Сorrelation between age and the intensity of the post-vaccination humoral immune response in individuals passed COVID-19. Immunologiya. 2022; 43 (5): 583–92. DOI: https://doi.org/10.33029/0206-4952-2022-43-5-583-592 (in Russian)

7. Nechay K.O., Andreev A.I., Andreev I.V., Esaulova D.R., Baklakova O.S., Shadyzheva M.B., Romanova L.V., Gegechkori V.I., Cherchenko N.G., Vechorko V.I., Kofiadi I.A., Gudima G.O., Martynov A.I., Smirnov V.V., Kudlay D.A., Khaitov M.R. Dynamic assessment of the intensity of the immune response to SARS-CoV-2 infection and immunization against COVID-19 with the vaccine «Sputnik V». Immunologiya. 2023; 44 (2): 157–66. DOI: https://doi.org/10.33029/0206-4952-2023-44-2-157-166 (in Russian)

8. Almeida A.J., Alpar HO. Nasal delivery of vaccines. J Drug Target. 1996; 3 (6): 455–67. DOI: https://doi.org/10.3109/10611869609015965

9. Boyaka P.N., Tafaro A., Fischer R., Leppla S.H., Fujihashi K., McGhee J.R. Effective mucosal immunity to anthrax: neutralizing antibodies and Th cell responses following nasal immunization with protective antigen. J Immunol. 2003; 170 (11): 5636–43. DOI: https://doi.org/10.4049/jimmunol.170.11.5636

10. Neutra M.R., Kozlowski P.A. Mucosal vaccines: the promise and the challenge. Nature Rev Immunol. 2006; 6: 149–58. DOI: https://doi.org/10.1038/nri1777

11. Khaitov R.M., Pinegin B.V., Pashenkov M.V. Epithelial cells of the respiratory tract as equal participants of innate immunity and potential targets for immunotropic drugs. Immunologiya. 2020; 41 (2): 107–13. DOI: https://doi.org/10.33029/0206-4952-2020-41-2-107-113 (in Russian)

12. Pinegin B.V., Pashenkov M.V., Pinegin V.B., Khaitov R.M. Mucosal epithelial cells and novel approaches to immunoprophylaxy and immunotherapy of infectious diseases. Immunologiya. 2020; 41 (6): 486–500. DOI: https://doi.org/10.33029/0206-4952-2020-41-6-486-500 (in Russian)

13. Kiyono H., Fukuyama S. NALT-versus Peyer’s-patch-mediated mucosal immunity. Nat Rev Immunol. 2004; 4: 699–710. DOI: https://doi.org/10.1038/nri1439

14. Channappanavar R., Zhao J., Perlman S. T cell-mediated immune response to respiratory coronaviruses. Immunol Res. 2014; 59 (1-3): 118–28. DOI: https://doi.org/10.1007/s12026-014-8534-z

15. Tan W., Lu Y., Zhang J., Wang J., Dan Y., Tan Zh., He X., Qian Ch., Sun Q., Hu Q., Liu H., Ye S., Xiang X., Zhou Y., Zhang W., Guo Y., Wang X., He W., Wan X., Sun F., Wei Q., Chen C., Pan G., Xia J., Mao Q., Chen Y., Deng G. Viral kinetics and antibody responses in patients with COVID-19. MedRxiv. 2020. URL: https://www.medrxiv.org/content/10.1101/2020.03.24.20042382v1 (date of access 13 June 2024)

16. Ibarrondo F.J., Fulcher J.A., Goodman-Meza D., Elliott J., Hofmann C., Hausner M.A., Ferbas K.G., Tobin N.H., Aldrovandi G.M., Yang O.O. Rapid decay of anti-SARSCoV-2 antibodies in persons with mild COVID-19. N Engl J Med. 2020; 383 (11): 1085–7. DOI: https://doi.org/10.1056/NEJMc2025179

17. Poteryaev D.A., Abbasova S.G., Ignatyeva P.E., Strizhakova O.M., Kolesnik S.V., Khamitov R.A. Assessment of T-cell immunity to SARS-CoV-2 in COVID-19 convalescents and vaccinated subjects, using TigraTest® SARS-CoV-2 ELISPOT kit. BIOpreparations. Prevention, Diagnosis, Treatment. 2021; 21 (3): 178–92. DOI: https://doi.org/10.30895/2221-996X-2021-21-3-178-192 (in Russian)

18. Lyagoskin I.V., Kargopolova P.E., Obyedkov D.A., Egorova I.Y., Shukurov R.R. Intra-laboratory validated «TigraTest® SARS-CoV-2» – test assessing release of interferon gamma in vitro to identify peripheral blood T-lymphocytes specifically responding against SARS-CoV-2 virus antigens. Russian Journal of Infection and Immunity. 2022; 12 (4): 701–3. DOI: https://doi.org/10.15789/2220-7619-ILV-1855 (in Russian)

19. R Core Team. R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing. 2020. URL: https://www.R-project.org (date of access 13 June 2024)

20. Jiang Y., Wu Q., Song P., You C. The Variation of SARS-CoV-2 and Advanced Research on Current Vaccines. Front Med (Lausanne). 2022; 8: 806641. DOI: https://doi.org/10.3389/fmed.2021.806641

21. Heinz F.X., Stiasny K. Distinguishing features of current COVID-19 vaccines: knowns and unknowns of antigen presentation and modes of action. NPJ Vaccines. 2021; 6: 104. DOI: https://doi.org/10.1038/s41541-021-00369-6

22. Lombardi A., Bozzi G., Ungaro R., Villa S., Castelli V., Mangioni D., Muscatello A., Gori A., Bandera A. Mini Review Immunological Consequences of Immunization with COVID-19 mRNA Vaccines: Preliminary Results. Front Immunol. 2021; 12: 657711. DOI: https://doi.org/10.3389/fimmu.2021.657711

23. Altmann D.M., Boyton R.J. SARS-CoV-2 T cell immunity: specificity, function, durability, and role in protection. Science Immunology. 2020; 5 (49): eabd6160. DOI: http://doi.org/10.1126/sciimmunol.abd6160

24. Swadling L., Maini M.K. T cells in COVID-19 – united in diversity. Nat Immunol. 2020; 21 (11): 1307–8. DOI: http://doi.org/10.1038/s41590-020-0798-y

25. Pashenkov M.V., Khaitov M.R. Immune response against epidemic coronaviruses. Immunologiya. 2020; 41 (1): 5–18. DOI: https://doi.org/10.33029/0206-4952-2020-41-1-5-18 (in Russian)

26. Astakhova E.A., Byazrova M.G., Milyaev S.M., Sukhova M.M., Mikhailov A.A., Morozov A.A., Prilipov A.G., Filatov A.V. Flow cytometric assay for the detection of anti-SARS-CoV-2 Spike antibodies in serum of vaccinated volunteers. Immunologiya. 2022; 43 (4): 447–57. DOI: https://doi.org/10.33029/0206-4952-2022-43-4-447-457 (in Russian)

27. Todryk S.M., Pathan A.A., Keating S., Porter D.W., Berthoud T., Thompson F., Klenerman P., Hill A.V.S. The relationship between human effector and memory T cells measured by ex vivo and cultured ELISPOT following recent and distal priming. Immunology. 2009; 128: 83–91. DOI: https://doi.org/10.1111/j.1365-2567.2009.03073.x

28. Singh G.R., Kaur K., Matariya R., Singh B., Sood R., Singh J. Intranasal (IN) COVID-19 vaccines – a breakthrough. Rocz Panstw Zakl Hig. 2023; 74 (1): 15–8. DOI: https://doi.org/10.32394/rpzh.2023.0251

All articles in our journal are distributed under the Creative Commons Attribution 4.0 International License (CC BY 4.0 license)

JOURNALS of «GEOTAR-Media»