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1 . 2025
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Trained immunity and heterologous protection against COVID-19 in risk groups

Abstract

Agonists of pattern-recognition receptors (PRR) cause stable epigenetic and metabolic alterations in innate immune cells resulting in long-lasting enhancement of responsiveness to secondary stimulation of the same or other PRRs. This altered responsiveness, termed trained immunity, may underlie non-specific protective effects of vaccines (heterologous protection). The COVID-19 pandemic offered great opportunities for testing the efficacy of trained immunity as an anti-infection defense strategy. However, despite promising preliminary data, randomized clinical trials (RCT) of BCG vaccine as a means to prevent COVID-19 in elderly people, persons with comorbidities and healthcare workers yielded mostly negative results. Lack of success of most RCT might have been caused by insufficiently intense vaccination schemes. Available laboratory data do not support a conclusion that BCG-induced heterologous protection against COVID-19 observed in some RCT is mediated by trained immunity. However, trained immunity may improve efficacy of specific anti-COVID-19 vaccines.

Keywords: innate immunity; trained immunity; BCG vaccine; COVID-19

For citation: Pashenkov M.V., Masyutina A.M. Trained immunity and heterologous protection against COVID-19 in risk groups. Immunologiya. 2025; 46 (1): 73–85. DOI: https://doi.org/10.33029/1816-2134-2025-46-1-73-85 (in Russian)

Funding. This work was supported by the state assignment from FMBA of Russia (code «Stareniye kletki-24»; code number 22.007.24.800). Open publication is allowed.

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

Authors’ contribution. Analysis of literature, writing the article – Pashenkov M.V., analysis of literature, editing the article – Masyutina A.M.

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