Studying the Impact of Psychophysiological Factors on the Immune Response to Vaccination

Relevance. Psychoneuroimmune aspects of the formation of post-vaccination immunity against SARS-CoV-2 are of particular interest for modern virology and epidemiology. The variability of the individual immune response to vaccination may be associated not only with immunological but also with psychophysiological factors. The aim to evaluate the influence of psychophysiological factors (situational and personal anxiety, awareness of vaccination) on the manifestation of the immune response after immunization with a vaccine for the prevention of COVID-19 based on virus-like particles (VLP), as well as to evaluate the relationships between these factors. Materials and methods. A questionnaire was administered to 248 volunteers aged 18 to 60 years to assess sociodemographic characteristics and analyze the level of awareness of vaccination issues. The level of anxiety was determined by the standardized State-Trait Anxiety Inventory (STAI) questionnaire adapted by C.D. Spielberger. The intensity of humoral immunity was also assessed before and after vaccination using enzyme-linked immunosorbent assay. All data were processed in encrypted form using the V1 cryptographic protocol to ensure blinding of the study. The transfer of intermediate data were carried out in accordance with the approved form provided in the clinical trial protocol. The study was conducted with the voluntary informed consent of the patients. The study protocol was approved at a meeting of the Ethics Council of the Department of Regulation of the Circulation of Medicines and Medical Devices of the Ministry of Health of the Russian Federation (№4293530-25-2ЭС-214.08.2025). Results. In the group of volunteers immunized with the VLP vaccine for COVID-19 prevention, there was a significant increase in the antibody titer (p<0.001), along with an increase in the level of situational anxiety (p<0.001). It is noteworthy that an increase in the antibody level by 4 times or more was noted in 90% of volunteers with a low level of state anxiety, while 100% of volunteers with a high level of state anxiety did not have an increase in the antibody titer. Factor analysis identified two components influencing post-vaccination humoral immunity: 1–"Anxiety", which included personal anxiety and state anxiety before and after vaccination (psychophysiological determinants); 2–"Immune-age profile", which included age and antibody titer level at the time of vaccination (biological determinants). The total cumulative contribution of the two components to the total variance was 59.7%. The increase in antibodies had a negative correlation with age and the initial level of antibodies (τ = -0,267; p < 0,00; 95% CI [-0,379; -0,141]; n = 156), while the anxiety level had a negative correlation with the degree of awareness of vaccination (τ = -0,212; p < 0,001; 95% CI [-0,324; -0,095]; n=156). For the first time, a predictive model based on discriminant analysis was obtained. Group membership by anxiety level was used as a classification criterion, and personal anxiety indicators, degree of awareness and age served as predictors. Conclusion. Elevated situational anxiety at the time of vaccination is a risk factor for a diminished post-vaccination humoral immune response. A predictive model has been developed to assess this risk, with patient knowledge being its key modifiable parameter. Targeted enhancement of knowledge about vaccine prophylaxis serves as a practical tool of a personalized approach, aimed at reducing anxiety and increasing vaccination efficacy. Ultimately, this strategy may boost both individual vaccine uptake and the overall public health impact of immunization programs.

1. Cohen S. Psychosocial vulnerabilities to upper respiratory infectious illness: Implications for susceptibility to coronavirus disease 2019 (COVID-19). Perspectives on Psychological Science. 2021;16(1):161–74. doi: 10.1177/1745691620942516

2. Holman E., Thompson R., Garfin D. et al. The unfolding COVID-19 pandemic: A probability-based, nationally representative study of mental health in the United States. Science Advances. 2020;6(42):eabd5390 doi: 10.1126/sciadv.abd5390

3. Kuznetsov A.P., Smelysheva L.N. Neuroendokrinnye mekhanizmy stress-reaktsii. Vestnik Kurganskogo gosudarstvennogo universiteta. 2006;6(2):5–10. (In Russ).

4. Pedersen A. F., Zachariae R., Bovbjerg D. H. Psychological stress and antibody response to influenza vaccination: a meta-analysis. Brain, behavior, and immunity. 2009;23(4):427–33. doi: 10.1016/j.bbi.2009.01.004

5. Phillips A. C. The vaccination model in psychoneuroimmunology research: a review. In: Psychoneuroimmunology: methods and protocols; 2012. P. 355–70.

6. Belousova Ya.D., Rafalsky V.V., Kislova E.D. Specifics of motivation of volunteers participating in in a clinical trial of the COVID-19 vaccine. Good Clinical Practice. 2022;4:4–12. (In Russ). doi: 10.37489/2588-0519-2022-4-4-12

7. Spielberger C. D. State-trait anxiety inventory for adults. (STAI-AD) [Database record]. APA PsycTests. 1983. https://doi.org/10.1037/t06496-000

8. Spielberger Ch.D., Khanin Yu.L. Shkala otsenki urovnya reaktivnoi i lichnostnoi trevozhnosti. Karelin A.A. Psikhologicheskie testy. 2000;1:39–45. (In Russ).

9. Plotnikov A.A., Zaykova O.N., Rusakova E.V., et al. Social epidemiology: relevance, approaches, main directions and development trends. Zdorovʹe naseleniâ i sreda obitaniâ. 2025;33(1):61–72. (In Russ). doi: 10.35627/2219-5238/2025-33-1-61-72

10. Vai B., Mazza M.G., Delli Colli C., et al. Mental disorders and risk of COVID-19-related mortality, hospitalisation, and intensive care unit admission: A systematic review and meta-analysis. The Lancet Psychiatry. 2021;8(9):797–812. doi: 10.1016/S2215-0366(21)00232-7

11. Wang Q., Xu R., Volkow N.D. Increased risk of COVID-19 infection and mortality in people with mental disorders: Analysis from electronic health records in the United States. World Psychiatry: Official Journal of the World Psychiatric Association (WPA). 2021;20(1):124–30. doi: 10.1002/wps.20806

12. Bower J.E., Kuhlman K.R., Haydon M.D., et al. Cultivating a healthy neuro-immune network: A health psychology approach. Social and Personality Psychology Compass. 2019;13(9):e12498. doi: 10.1111/spc3.12498

13. Barrett T. J., Corr E. M., van Solingen C., et al. Chronic stress primes innate immune responses in mice and humans. Cell reports. 2021;36(10): 109595. doi: 10.1016/j.celrep.2021.109595

14. Dai S, Mo Y, Wang Y., et al. Chronic stress promotes cancer development. Front Oncol. 2020;10:1492. doi: 10.3389/fonc.2020.01492.

15. Diez Roux AV. Social epidemiology: Past, present, and future. Annu Rev Public Health. 2022;43:79–98. doi: 10.1146/annurev-publhealth-060220-042648

16. Li Z., Sun X. Social factors influencing behavioral intentions to vaccinate: personality traits and cues to action. Frontiers in Psychology. 2025;16:1481147. doi: 10.3389/fpsyg.2025.1481147

17. Guerrero-Araya E., Ravello, C., Rosemblatt, M., et al. Socioeconomic status correlates with COVID-19 vaccination coverage among primary and secondary students in the most populated city of Chile. Scientific Reports. 2025;15(1):1509. doi: 10.1038/s41598-024-84260-z

18. Reis, M., Michalski, N., Bartig, S., et al. Reconsidering inequalities in COVID-19 vaccine uptake in Germany: a spatiotemporal analysis combining individual educational level and area-level socioeconomic deprivation. Scientific Reports. 2024;14(1):23904. doi: 10.1038/s41598-024-75273-9

19. Plakida AV, Briko NI, Namazova-Baranova LS, et al. Increasing population adherence to vaccination: evaluation and a systematic approach to implementation. Epidemiology and Vaccinal Prevention. 2022;21(3):4–26 (In Russ.). doi:10.31631/2073-3046-2022-21-3-4-26

20. Briko NI, Feldblyum IV. The Modern Concept of Development of Vaccine Prevention in Russia. Epidemiology and Vaccinal Prevention. 2019; 18 (5): 4–13. (In Russ.). doi: 10.31631/2073-3046-2019-18-5-4-13.