Humoral immune response and serological profile of autoantibodies in heart transplant recipients after vaccination against coronavirus infection.

Due to the mandatory immunosuppression and concomitant diseases, heart transplant recipients are at an increased risk of an adverse outcome from COVID-19 infection. The efficacy and safety of using vaccines to prevent COVID-19 infection in patients with heart transplants, including the development of undesirable inflammatory and autoimmune reactions, has not been sufficiently studied. This paper presents the characteristics of humoral immunity and the analysis of autoantibody production in heart transplant recipients after vaccination against a coronavirus infection. The main group consisted of patients (n = 40) who underwent orthotopic heart transplantation in the period from 2009 to 2021 at the National Research and Practical Center “Cardiology” and received two doses of the Vero Cell vaccine (China) or got a three-step booster Gam-COVID-Vac (Sputnik V, Russian Federation). It has been shown that 63 % of vaccinated individuals with no previous COVID-19 history and 85 % of patients with a history of COVID-19 infection developed humoral post-vaccination immunity. The humoral response in patients who had seroconversion prior to vaccination exhibited elevated levels of virusspecific IgG antibodies to the SARS-CoV-2 virus S protein during the post-vaccination period, with a statistically significant increase observed by 9–12 months after booster vaccination. Vaccination against the coronavirus infection does not result in an increase of serum autoantibodies (RF IgG and IgA, anti-SSR, cardiolipin IgG, β2-glycoprotein IgG, ANA, ANCA-Pro, anti-SLA/LP, anti-GD-IgA) in heart transplant recipients. At the same time, vaccinated heart transplant recipients with a history of coronavirus infection showed an increase in the level of antibodies to IFN-α for a period of 9–12 months after the main vaccination. This evidence, when associated with HLA alleles, must be taken into account for identifying patients who may be at risk of developing severe diseases.

1. Tang K., Wu X., Luo Y., Wei Z., Feng L., Wu L. Meta-analysis of immunologic response after COVID-19 mRNA vaccination in solid organ transplant recipients. Journal of Infection, 2022, vol. 84, no. 5, pp. 73–75. https://doi.org/10.1016/j. jinf.2022.02.016

2. Israr J., Kumar A. Introduction to COVID-19 vaccines and kidney transplant recipient. OBM Transplantation, 2025, vol. 9, no. 1, pp. 236–258. https://doi.org/10.21926/obm.transplant.2501236

3. Boyarsky B. J., Werbel W. A., Avery R. K., Tobian A. R., Massie A. B., Segev D. L., Garonzik-Wang J. M. Antibody response to 2-dose SARS-CoV-2 mRNA vaccine series in solid organ transplant recipients. Journal of the American Medical Association, 2021, vol. 325, no. 21, pp. 2204–2206. https://doi.org/10.1001/jama.2021.7489

4. Zhuo R., Charlton C., Plitt S., Thompson L. A., Braun S., Day J., Osiowy C., Tipples G., Kanji J. N. Comparison of SARS-CoV-2 spike antibody quantitative titer reporting using the World Health Organization International Standard Units by four commercial assays. Journal of Clinical Virology, 2022, vol. 156, art. 105292. https://doi.org/10.1016/j.jcv.2022.105292

5. Ravanan R., Mumford L., Ushiro-Lumb I., Callaghan C., Pettigrew G., Thorburn D., Gardiner D., Forsythe J. Two doses of SARS-CoV-2 vaccines reduce risk of death due to COVID-19 in solid organ transplant recipients: preliminary outcomes from a UK registry linkage analysis. Transplantation, 2021, vol. 105, no. 11, pp. 263–264. https://doi.org/10.1097/TP.0000000000003908

6. Aslam S., Adler E., Mekeel K., Little S. J. Clinical effectiveness of COVID-19 vaccination in solid organ transplant recipients. Transplant Infectious Disease, 2021, vol. 23, no. 5, art. e13705. https://doi.org/10.1111/tid.13705

7. Rodríguez Y., Rojas M., Beltrán S., Polo F., Camacho-Domínguez L., Morales S. D., Gershwin M. E., Anaya J.-M. Autoimmune and autoinflammatory conditions after COVID-19 vaccination. New case reports and updated literature review. Journal of Autoimmunity, 2022, vol. 132, art. 102898. https://doi.org/10.1016/j.jaut.2022.102898

8. Segal Y., Shoenfeld Y. Vaccine-induced autoimmunity: the role of molecular mimicry and immune crossreaction. Cellular and Molecular Immunology, 2018, vol. 15, no. 6, pp. 586–594. https://doi.org/10.1038/cmi.2017.151

9. Dotan A., Muller S., Kanduc D., David P., Halpert G., Shoenfeld Y. The SARS-CoV-2 as an instrumental trigger of autoimmunity. Autoimmunity Reviews, 2021, vol. 20, no. 4, art. 102792. https://doi.org/10.1016/j.autrev.2021.102792

10. Belskaya I. V., Amvrosieva T. V., Bohush Z. F., Paklonskaya N. V., Anisko L. A., Rogacheva T. A. Humoral immunity against different SARS-CoV-2 variants. Laboratornaya diagnostika. Vostochnaya Evropa = Laboratory Diagnostics. Eastern Europe, 2023, vol. 12, no. 4, pp. 523–535 (in Russian). https://doi.org/10.34883/PI.2023.12.4.004

11. Sizyakina L. P., Andreeva I. I., Kharitonova M. V., Zaitseva N. S., Lyubimov D. S., Zakurskaya V. Ya., Totolian A. A. Mechanisms of formation of hybrid immunity in people who recovered from COVID-19 and were vaccinated with SARSCoV-2 peptide antigens. Meditsinskaya immunologiya = Medical Immunology, 2022, vol. 24, no. 3, pp. 629–640 (in Russian). https://doi.org/10.15789/1563-0625-MOF-2490

12. Keijzer S., Oskam N., Ooijevaar-de Heer P., Steenhuis M., Keijser J. B. D., Wieske L., van Dam K. P. J., Stalman E. W., Kummer L. Y. L., Boekel L., Kuijpers T. W., ten Brinke A., van Ham S. M., Eftimov F., Tas S. W., Wolbink G. J., Rispens T. Longitudinal rheumatoid factor autoantibody responses after SARS-CoV-2 vaccination or infection. Frontiers in Immunology, 2024, vol. 15, art. 1314507. https://doi.org/10.3389/fimmu.2024.1314507

13. Goncalves D., Mezidi M., Bastard P., Perret M., Saker K., Fabien N., Pescarmona R., Lombard C., Walzer T., Casanova J.-L., Belot A., Richard J.-C., Trouillet-Assant S. Antibodies against type I interferon: detection and association with severe clinical outcome in COVID-19 patients. Clinical and Translational Immunology, 2021, vol. 10, no. 8, art. e1327. https://doi. org/10.1002/cti2.1327

14. Raadsen M. P., Gharbharan A., Jordans C. C. E., Mykytyn A. Z., Lamers M. M., van den Doel P. B., Endeman H., van den Akker J. P. C., GeurtsvanKessel C. H., Koopmans M. P. G., Rokx C., Goeijenbier M., van Gorp E. C. M., Rijnders B. J. A., Haagmans B. L. Interferon-α2 auto-antibodies in convalescent plasma therapy for COVID-19. Journal of Clinical Immunology, 2022, vol. 42, no. 2, pp. 232–239. https://doi.org/10.1007/s10875-021-01168-3