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Fiction and Facts about BCG Imparting Trained Immunity against COVID-19

ABSTRACT: The Bacille Calmette-Guérin or BCG vaccine, the only vaccine available against Mycobacterium tuberculosis can induce a marked Th1 polarization of T-cells, characterized by the antigen-specific secretion of IFN-γ and enhanced antiviral response. A number of studies have supported the concept of protection by non-specific boosting of immunity by BCG and other microbes. BCG is a well-known example of a trained immunity inducer since it imparts ‘non-specific heterologous’ immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the recent pandemic. SARS-CoV-2 continues to inflict an unabated surge in morbidity and mortality around the world. There is an urgent need to devise and develop alternate strategies to bolster host immunity against the coronavirus disease of 2019 (COVID-19) and its continuously emerging variants. Several vaccines have been developed recently against COVID-19, but the data on their protective efficacy remains doubtful. Therefore, urgent strategies are required to enhance system immunity to adequately defend against newly emerging infections. The concept of trained immunity may play a cardinal role in protection against COVID-19. The ability of trained immunity-based vaccines is to promote heterologous immune responses beyond their specific antigens, which may notably help in defending against an emergency situation such as COVID-19 when the protective ability of vaccines is suspicious. A growing body of evidence points towards the beneficial non-specific boosting of immune responses by BCG or other microbes, which may protect against COVID-19. Clinical trials are underway to consider the efficacy of BCG vaccination against SARS-CoV-2 on healthcare workers and the elderly population. In this review, we will discuss the role of BCG in eliciting trained immunity and the possible limitations and challenges in controlling COVID-19 and future pandemics.

SUBMITTER: Kaur G

PROVIDER: S-EPMC9316941 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUNDThe antituberculosis vaccine bacillus Calmette-Guérin (BCG) reduces overall infant mortality. Induction of innate immune memory, also termed trained immunity, contributes toward protection against heterologous infections. Since immune cells display oscillations in numbers and function throughout the day, we investigated the effect of BCG administration time on the induction of trained immunity.METHODSEighteen volunteers were vaccinated with BCG at 6 pm and compared with 36 age- and sex-matched volunteers vaccinated between 8 am and 9 am. Peripheral blood mononuclear cells were stimulated with Staphylococcus aureus and Mycobacterium tuberculosis before, as well as 2 weeks and 3 months after, BCG vaccination. Cytokine production was measured to assess the induction of trained immunity and adaptive responses, respectively. Additionally, the influence of vaccination time on induction of trained immunity was studied in an independent cohort of 302 individuals vaccinated between 8 am and 12 pm with BCG.RESULTSCompared with evening vaccination, morning vaccination elicited both a stronger trained immunity and adaptive immune phenotype. In a large cohort of 302 volunteers, early morning vaccination resulted in a superior cytokine production capacity compared with later morning. A cellular, rather than soluble, substrate of the circadian effect of BCG vaccination was demonstrated by the enhanced capacity to induce trained immunity in vitro in morning- compared with evening-isolated monocytes.CONCLUSIONSBCG vaccination in the morning induces stronger trained immunity and adaptive responses compared with evening vaccination. Future studies should take vaccine administration time into account when studying specific and nonspecific effects of vaccines; early morning should be the preferred moment of BCG administration.FUNDINGThe Netherlands Organization for Scientific Research, the European Research Council, and the Danish National Research Foundation.

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Fiction and Facts about BCG Imparting Trained Immunity against COVID-19

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