Induction of Trained Immunity by BCG: Recent Data and Opinions

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Abstract

Bacillus Calmette-Guerin (BCG), developed in the early 20th century to protect against tuberculosis, is one of the most widely used vaccines in the world. In addition to protecting against tuberculosis, this vaccine has also been shown to reduce the risk of various other infections. During the COVID-19 pandemic, it was found that BCG-vaccinated health care workers had lower detection rates of the SARS-CoV-2 virus compared to unvaccinated individuals. This appears to be due to the generation of trained immunity (TRIM) and non-specific protective effects (NSE), which are likely attributed to the epigenetic and metabolic reprogramming of innate immune cells, known as trained immunity. NSE further holds promise for the development of future therapeutics that can protect against unpredictable pandemics. Additionally, TRIM inducers provide new perspectives on improving the efficacy of standard vaccines by incorporating them into vaccine formulations to enhance both specific and nonspecific immune responses.

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About the authors

I. V. Alekseenko

National Research Center “Kurchatov Institute”; Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences

Email: edsverd@gmail.com
Russian Federation, Moscow, 123182; Moscow, 117997

L. G. Kondratyeva

National Research Center “Kurchatov Institute”; Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences

Author for correspondence.
Email: edsverd@gmail.com
Russian Federation, Moscow, 123182; Moscow, 117997

I. P. Chernov

Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences

Email: edsverd@gmail.com
Russian Federation, Moscow, 117997

E. D. Sverdlov

National Research Center “Kurchatov Institute”

Email: liakondratyeva@yandex.ru
Russian Federation, Moscow, 123182

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2. Fig. 1. Trained immunity is mediated by metabolic and epigenetic remodeling in innate immune cells that results in increased gene transcription and host defense against heterologous pathogens. Following the first exposure to a live or live attenuated pathogen, the innate immune response enters a “trained” state, ready to be amplified following a second infection. A naive, unstimulated cell (1) exhibits highly condensed chromatin. Its primary stimulation results in epigenetic modifications of chromatin (such as histone acetylation (Ac) or methylation (Me)) that promote chromatin unfolding and facilitate gene transcription (2). These epigenetic changes may persist or may be only partially reversed after the stimulus has ceased (3) and may thus generate robust and memorizable innate immune memory that is elicited in response to a secondary inflammatory stimulus (4) (based on [5, 26, 27]).

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