BCG-induced trained immunity: can it offer protection against COVID-19?

Luke A J O'Neill, Mihai G Netea, Luke A J O'Neill, Mihai G Netea

Abstract

Bacillus Calmette–Guérin (BCG) vaccination has been reported to decrease susceptibility to respiratory tract infections, an effect proposed to be mediated by the general long-term boosting of innate immune mechanisms, also termed trained immunity. Here, we discuss the non-specific beneficial effects of BCG against viral infections and whether this vaccine may afford protection to COVID-19.

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1. Trained immunity antiviral host defence.
Fig. 1. Trained immunity antiviral host defence.
a | Bacillus Calmette–Guérin (BCG) vaccination has been shown to protect against multiple viral pathogens, including respiratory syncytial virus (RSV), influenza A virus and herpes simplex virus type 2 (HSV2). Will it protect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)? b | Trained immunity leading to enhanced innate immune responses to different pathogens after a vaccination is mediated by metabolic and epigenetic rewiring in innate immune cells, which leads to increased gene transcription and improved host defence. c | Trained immunity as a tool for enhancing population immunity during a pandemic ahead of the availability of a specific vaccine. TNF, tumour necrosis factor.

References

    1. Huang C, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497–506. doi: 10.1016/S0140-6736(20)30183-5.
    1. Shann F. The non-specific effects of vaccines. Arch. Dis. Child. 2010;95:662–667. doi: 10.1136/adc.2009.157537.
    1. Aaby P, et al. Randomized trial of BCG vaccination at birth to low-birth-weight children: beneficial nonspecific effects in the neonatal period? J. Infect. Dis. 2011;204:245–252. doi: 10.1093/infdis/jir240.
    1. Stensballe LG, et al. Acute lower respiratory tract infections and respiratory syncytial virus in infants in Guinea-Bissau: a beneficial effect of BCG vaccination for girls community based case-control study. Vaccine. 2005;23:1251–1257. doi: 10.1016/j.vaccine.2004.09.006.
    1. Wardhana, et al. The efficacy of Bacillus Calmette-Guerin vaccinations for the prevention of acute upper respiratory tract infection in the elderly. Acta Med. Indones. 2011;43:185–190.
    1. Ohrui T, et al. Prevention of elderly pneumonia by pneumococcal, influenza and BCG vaccinations [Japanese] Nihon Ronen Igakkai Zasshi. 2005;42:34–36. doi: 10.3143/geriatrics.42.34.
    1. Nemes E, et al. Prevention of M. tuberculosis infection with H4:IC31 vaccine or BCG revaccination. N. Engl. J. Med. 2018;379:138–149. doi: 10.1056/NEJMoa1714021.
    1. Spencer JC, Ganguly R, Waldman RH. Nonspecific protection of mice against influenza virus infection by local or systemic immunization with Bacille Calmette-Guerin. J. Infect. Dis. 1977;136:171–175. doi: 10.1093/infdis/136.2.171.
    1. Starr SE, et al. Effects of immunostimulants on resistance of newborn mice to herpes simplex type 2 infection. Proc. Soc. Exp. Biol. Med. 1976;152:57–60. doi: 10.3181/00379727-152-39327.
    1. Ikeda S, Negishi T, Nishimura C. Enhancement of non-specific resistance to viral infection by muramyldipeptide and its analogs. Antivir. Res. 1985;5:207–215. doi: 10.1016/0166-3542(85)90025-7.
    1. Moorlag S, et al. Non-specific effects of BCG vaccine on viral infections. Clin. Microbiol. Infect. 2019;25:1473–1478. doi: 10.1016/j.cmi.2019.04.020.
    1. Kleinnijenhuis J, et al. Bacille Calmette-Guerin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes. Proc. Natl Acad. Sci. USA. 2012;109:17537–17542. doi: 10.1073/pnas.1202870109.
    1. Netea MG, et al. Trained immunity: a program of innate immune memory in health and disease. Science. 2016;352:aaf1098. doi: 10.1126/science.aaf1098.
    1. Arts RJW, et al. BCG vaccination protects against experimental viral infection in humans through the induction of cytokines associated with trained immunity. Cell Host Microbe. 2018;23:89–100. doi: 10.1016/j.chom.2017.12.010.
    1. Gursel M, Gursel I. Is global BCG vaccination-induced trained immunity relevant to the progression of SARS-CoV-2 pandemic? Allergy. 2020 doi: 10.1111/all.14345.
    1. Mehta P, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395:1033–1034. doi: 10.1016/S0140-6736(20)30628-0.

Source: PubMed

Sponzoři a spolupracovníci

Zdravotní podmínky

Drogové intervence

3
Předplatit