1 . 2022

Post-vaccination and post-infection humoral immune response to the SARS-CoV-2 infection

Abstract

Introduction. Mass vaccination of the population against SARS-CoV-2 in Russia and abroad has been going on for more than 2 years. Various types of vaccines are used for vaccination (vector vaccines, RNA vaccines, whole-virion vaccines). The first in the world was registered the Russian vector vaccine «Gam-COVID-Vac» («Sputnik V»), which is widely used in our country, as well as in many other countries of the world. An important area of research is the monitoring of the parameters of the vaccine-induced immune response their analysis in relation to the characteristics of the immune response caused by SARS-CoV-2 infection/COVID-19. Such studies are important both for assessing the intensity and duration of post-vaccination immunity, and for improving strategies for immunoprophylaxis and immunotherapy of coronavirus infection. The article presents the results of a study of the humoral immune response in patients with COVID-19 and vaccinated with «Sputnik V» in the period from autumn 2020 till the present time.

The aim of the work – a comparative study of the humoral immune response to SARS-CoV-2 infection and vaccination against COVID-19.

Material and methods. The content of antibodies against SARS-CoV-2 S- and N-proteins was studied in 449 blood serum samples of men and women (age 25–65 years). 5 groups of samples were formed: suffered from COVID-19 of mild and moderate severity, at different times after recovery (262 samples); immunized with the «Sputnik V» vaccine, at different times after injection of the 2^nd component of «Sputnik V» (104 samples); suffered from COVID-19 of mild and moderate severity, and then vaccinated with «Sputnik V» (53 samples); vaccinated with «Sputnik V», and then suffered with COVID-19 (12 samples); revaccinated with the vaccine «Sputnik Light» (18 samples).

Results. To assess the content of IgG antibodies to S-protein and to N-protein of SARS-CoV-2 in human blood sera, an EIA diagnostic system was developed further certified by the Ministry of Health of Russian Federation. In people suffered COVID-19 in 90 % of cases the positive levels of IgG antibodies to SARS-CoV-2 S-protein persist 9 months after recovery, while the proportion of potential plasma donors and material for obtaining intravenous immunoglobulin with a high content of IgG antibodies to S-protein 1 month after the disease is 20 %. In 76 % of people vaccinated with «Sputnik V» high levels of IgG antibodies to S-protein are detected within 6 months after the course of vaccination. The content of IgG antibodies to S-protein in the blood sera of persons suffered COVID-19, and then 6 months after recovery vaccinated with the 1^st component of the vaccine «Sputnik V» in 100 % of cases was high with a positivity coefficient above 8.1, regardless of the initial value, already on 7 and 21 days after injection. In persons vaccinated with «Sputnik V» and then passed COVID-19, a high content of S-specific IgG antibodies is observed in 100 % of cases. The examination of vaccinated persons who underwent revaccination with «Sputnik Light» showed a 100 % high level of antibodies against S-protein.

Conclusion. The developed test system may be suitable for assessing the content of IgG antibodies to SARS-CoV-2 antigens in COVID-19 patients, vaccinated and revaccinated. The performed study demonstrated that there is a intensive post-vaccination immunity for 6 months and post-infectious immunity for 9 months.

Keywords:coronavirus infection; COVID-19; antibodies; post-infection immunity; post-vaccination immunity

For citation: 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)

Funding. The study had no sponsor support.

Conflict of interests. Authors declare no conflict of interests.

Authors contribution. Authors contributed equally to the writing of the article.

References

1. Convalescent Plasma EUA Letter of Authorization December 28, 2021. URL: https://www.fda.gov/media/141477/download

2. Temporary guidelines «Prevention, diagnosis and treatment of new coronavirus infection (COVID-19). Version 15 (22.02.2022)» (approved by the Ministry of Health of the Russian Federation). 2022, 245 р.

3. Sethuraman N., Jeremiah S.S., Ryo A. Interpreting diagnostic tests for SARS-CoV-2. JAMA. 2020; 323 (22): 2249–51. DOI: https://doi.org/10.1001/jama.2020.8259

4. Guo L., Ren L., Yang S., Xiao M., Chang D., Yang F., Cruz C.D., Wang Y., Wu C., Xiao Y., Zhang L., Han L., Dang S., Xu Y., Yang Q.W., Xu S.Y., Zhu H.D., Xu Y.C., Jin Q., Sharma L., Wang L., Wang J. Profiling early humoral response to diagnose novel coronavirus disease (COVID-19). Clinical Infectious Diseases. 2020; 71 (15): 778–85. DOI: https://doi.org/10.1093/cid/ciaa310

5. 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

6. Gaebler C., Wang Z., Lorenzi J.C.C., Muecksch F., Finkin S., Tokuyama M., Cho A., Jankovic M., Schaefer-Babajew D., Oliveira T.Y., Cipolla M., Viant C., Barnes C.O., Bram Y., Breton G., Hägglöf T., Mendoza P., Hurley A., Turroja M., Gordon K., Millard K.G., Ramos V., Schmidt F., Weisblum Y., Jha D., Tankelevich M., Martinez-Delgado G., Yee J., Patel R., Dizon J., Unson-O’Brien C., Shimeliovich I., Robbiani D.F., Zhao Z., Gazumyan A., Schwartz R.E., Hatziioannou T., Bjorkman P.J., Mehandru S., Bieniasz P.D., Caskey M., Nussenzweig M.C. Evolution of antibody immunity to SARS-CoV-2. Nature. 2021; 591 (7851): 639–44. DOI: https://doi.org/10.1038/s41586-021-03207-w

7. Gushchin V.A., Dolzhikova I.V., Shchetinin A.M., Odintsova A.S., Siniavin A.E., Nikiforova M.A., Pochtovyi A.A., Shidlovskaya E.V., Kuznetsova N.A., Burgasova O.A., Kolobukhina L.V., Iliukhina A.A., Kovyrshina A.V., Botikov A.G., Kuzina A.V., Grousova D.M., Tukhvatulin A.I., Shcheblyakov D.V., Zubkova O.V., Karpova O.V., Voronina O.L., Ryzhova N.N., Aksenova E.I., Kunda M.S., Lioznov D.A., Danilenko D.M., Komissarov A.B., Tkachuck A.P., Logunov D.Y., Gintsburg A.L. Neutralizing Activity of Sera from Sputnik V-Vaccinated People against Variants of Concern (VOC: B.1.1.7, B.1.351, P.1, B.1.617.2, B.1.617.3) and Moscow Endemic SARS-CoV-2 Variants. Vaccines. 2021; 9: 779. DOI: https://doi.org/10.3390/vaccines9070779

8. Lapa D., Grousova D.M., Matusali G., Meschi S., Colavita F., Bettini A., Gramigna G., Francalancia M., Garbuglia A.R., Girardi E., Puro V., Antinori A., Kovyrshina A.V., Dolzhikova I.V., Shcheblyakov D.V., Tukhvatulin A.I., Zubkova O.V., Logunov D.Y., Naroditsky B.S., Vaia F., Gintsburg A.L. Retention of Neutralizing response against SARS-CoV-2 Omicron variant in Sputnik V vaccinated individuals. medRxiv. 2022. DOI: https://doi.org/10.1101/2022.01.15.22269335

9. Molodtsov I.A., Kegeles E., Mitin A.N., Mityaeva O., Musatova O.E., Panova A.E., Pashenkov M.V., Peshkova I.O., Almaqdad A., Asaad W., Budikhina A.S., Deryabin A.S., Dolzhikova I.V., Filimonova I.N., Gracheva A.N., Ivanova O.I., Kizilova A., Komogorova V.V., Komova A., Kompantseva N.I., Lagutkin D.A., Lomakin Y.A., Maleeva A.V., Maryukhnich E.V., Mohammad A., Murugin V.V., Murugina N.E., Navoikova A., Nikonova M.F., Ovchinnikova L.A., Pinegina N.V., Potashnikova D.M., Romanova E.V., Saidova A.A., Sakr N., Samoilova A.G., Serdyuk Y., Shakirova N.T., Sharova N.I., Sheetikov S.A., Shemetova A.F., Shevkova L., Shpektor A.V., Trufanova A., Tvorogova A.V., Ukrainskaya V.M., Vinokurov A.S., Vorobyeva D.A., Zornikova K.V., Efimov G.A., Khaitov M.R., Kofiadi I.A., Komissarov A.A., Logunov D.Y., Naigovzina N.B., Rubtsov Y.P., Vasilyeva I.A., Volchkov P., Vasilieva E.. SARS-CoV-2 specific T cells and antibodies in COVID-19 protection: a prospective study. medRxiv. 2021. DOI: https://doi.org/10.1101/2021.08.19.21262278

10. Suthar M.S., Zimmerman M., Kauffman R., Mantus G., Linderman S., Vanderheiden A., Nyhoff L., Davis C.W., Adekunle O., Affer, Sherman M., Reynolds S., Verkerke H.P., Alter D.N., Guarner J., Bryksin J., M.C. Horwath, Arthur C.M., Saakadze N., Smith G.H., Edupuganti S., Scherer E.M., Hellmeister K., Cheng A., Morales J.A., Neish A.S., Stowell S.R., Frank F., Ortlund E., Anderson E.J., Menachery V.D., Rouphael N., Mehta A.K., Stephens D.S., Ahmed R., Roback J.D., Wrammert J. Rapid generation of neutralizing antibody responses in COVID-19 patients. Cell Reports Medicine. 2020; 1 (3): 100040. DOI: https://doi.org/10.1016/j.xcrm.2020.100040

11. Robbiani D.F., Gaebler C., Muecksch F., Lorenzi J.C.C., Wang Z., Cho A., Agudelo M., Barnes C.O., Gazumyan A., Finkin S., Hägglöf T., Oliveira T.Y., Viant C., Hurley A., Hoffmann H.H., Millard K.G., Kost R.G., Cipolla M., Gordon K., Bianchini F., Chen S.T., Ramos V., Patel R., Dizon J., Shimeliovich I., Mendoza P., Hartweger H., Nogueira L., Pack M., Horowitz J., Schmidt F., Weisblum Y., Michailidis E., Ashbrook A.W., Waltari E., Pak J.E., Huey-Tubman K.E., Koranda N., Hoffman P.R., West Jr A.P., Rice C.M., Hatziioannou T., Bjorkman P.J., Bieniasz P.D., Caskey M., Nussenzweig M.C. Convergent antibody responses to SARS-CoV-2 in convalescent individuals. Nature. 2020; 584 (7821): 437–42. DOI: https://doi.org/10.1038/s41586-020-2456-9

12. CoronaDerm-PS (CoronaSkinTest, recombinant coronavirus allergen). Permission to conduct clinical trials No. 90 dated 10.02.2022, study code CDPS-01/21, 2022.

13. Slogotskaya L.V., Litvinov V., Kudlay D.A., Ovsyankina E., Seltsovsky P., Ivanova D., Nikolenko N. New skin test with recombinant protein CFP10-ESAT6 in patients (children and adults) with tuberculosis, non-tuberculosis disease and latent TB infection. European Respiratory Journal. 2012; 40b(S56): 416.

14. Zakurskaya V.Ya., Sizyakina L.P., Kharitonova M.V., Shlyk S.V. Dynamics of specific humoral response in COVID-19 patients. Immunologiya. 2022; 43 (1): 71–7. DOI: https://doi.org/10.33029/0206-4952-2022-43-1-71-77

15. Dolzhikova I.V., Iliukhina A.A., Kovyrshina A.V., Kuzina A.V., Gushchin V.A., Siniavin A.E., Pochtovyi A.A., Shidlovskaya E.V., Kuznetsova N.A., Megeryan M.M., Dzharullaeva A.S., Erokhova A.S., Izhaeva F.M., Grousova D.M., Botikov A.G., Shcheblyakov D.V., Tukhvatulin A.I., Zubkova O.V., Logunov D.Y., Gintsburg A.L. Sputnik Light booster after Sputnik V vaccination induces robust neutralizing antibody response to B.1.1.529 (Omicron) SARS-CoV-2 variant. medRxiv. 2021. DOI: https://doi.org/10.1101/2021.12.17.21267976

16. Ikegame S., Siddiquey M., Hung C.T., Haas G., Brambilla L., Oguntuyo K.Y., Kowdle S., Chiu H. P., Stevens C. S., Vilardo A. E., Edelstein A., Perandones C., Kamil J. P., Lee B. Neutralizing activity of Sputnik V vaccine sera against SARS-CoV-2 variants. Nature communications. 2021; 12 (1): 4598. DOI: https://doi.org/10.1038/s41467-021-24909-9

17. Liu L., Iketani S., Guo Y., Chan J.F., Wang M., Liu L., Luo Y., Chu H., Huang Y., Nair M.S., Yu J., Chik K.K., Yuen T.T., Yoon C., To K.K., Chen H., Yin M.T., Sobieszczyk M.E., Huang Y., Wang H.H., Sheng Z., Yuen K.Y., Ho D.D. Striking Antibody Evasion Manifested by the Omicron Variant of SARS-CoV-2. Nature. 2021. DOI: https://doi.org/10.1038/s41586-021-04388-0

18. Skowronski D.M., De Serres G. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. The New England Journal of Medicine. 2021; 384: 1576–77. DOI: https://doi.org/10.1056/NEJMc2036242

19. Dejnirattisai W., Shaw R.H., Supasa P., Liu C., Stuart A.S., Pollard A.J., Liu X., Lambe T., Crook D., Stuart D.I., Mongkolsapaya J., Nguyen-Van-Tam J.S., Snape M.D., Screaton G.R., Com-COV2 study group. Reduced neutralisation of SARS-CoV-2 omicron B.1.1.529 variant by post-immunisation serum. The Lancet. 2021; 399 (10321): 234–6. DOI: https://doi.org/10.1016/S0140-6736(21)02844-0

20. Omicron: severity and VE Imperial College COVID-19 Response Team. 5th January 2022. URL: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1046479/S1479_Imperial_Severity.pdf.

21. Nogrady B. Mounting evidence suggests Sputnik COVID vaccine is safe and effective. Nature. 2021; 595 (7867): 339–40. DOI: https://doi.org/10.1038/d41586-021-01813-2

22. Komissarov A.A., Dolzhikova I.V., Efimov G.A., Logunov D.Y., Mityaeva O., Molodtsov I.A., Naigovzina N.B., Peshkova I.O., Shcheblyakov D.V., Volchkov P., Gintsburg A.L., Vasilieva E. Boosting of the SARS-CoV-2-Specific Immune Response after Vaccination with Single-Dose Sputnik Light Vaccine. The Journal of Immunology. 2022. DOI: https://doi.org/10.4049/jimmunol.2101052

23. Accorsi E.K., Britton A., Fleming-Dutra K.E., Smith Z.R., Shang N., Derado G., Miller J., Schrag S.J., Veran J.R. Association Between 3 Doses of mRNA COVID-19 Vaccine and Symptomatic Infection Caused by the SARS-CoV-2 Omicron and Delta Variants. JAMA. 2022; 327 (7): 639–51. DOI: https://doi.org/10.1001/jama.2022.0470

24. SARS-CoV-2 variants of concern and variants under investigation in England. UK Health Security Agency. Technical briefing 31. 2021. URL: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1042367/technical_briefing-31-10-december-2021.pdf