Abstract
The Bacillus Calmette-Guérin (BCG) is a live attenuated tuberculosis vaccine that has the ability to induce non-specific cross-protection against pathogens that might be unrelated to the target disease. Vaccination with BCG reduces mortality in newborns and induces an improved innate immune response against microorganisms other than Mycobacterium tuberculosis, such as Candida albicans and Staphylococcus aureus. Innate immune cells, including monocytes and natural killer (NK) cells, contribute to this non-specific immune protection in a way that is independent of memory T or B cells. This phenomenon associated with a memory-like response in innate immune cells is known as “trained immunity.” Epigenetic reprogramming through histone modification in the regulatory elements of particular genes has been reported as one of the mechanisms associated with the induction of trained immunity in both, humans and mice. Indeed, it has been shown that BCG vaccination induces changes in the methylation pattern of histones associated with specific genes in circulating monocytes leading to a “trained” state. Importantly, these modifications can lead to the expression and/or repression of genes that are related to increased protection against secondary infections after vaccination, with improved pathogen recognition and faster inflammatory responses. In this review, we discuss BCG-induced cross-protection and acquisition of trained immunity and potential heterologous effects of recombinant BCG vaccines.
Highlights
One of the leading causes of human death worldwide is tuberculosis (TB), a bacterial infection caused by Mycobacterium (M.) tuberculosis
The bacillus Calmette-Guérin (BCG) vaccine has been used in humans for almost a 100 years, proving its immunogenicity and safety
It is still unclear whether recombinant BCGs can induce trained immunity after vaccination
Summary
One of the leading causes of human death worldwide is tuberculosis (TB), a bacterial infection caused by Mycobacterium (M.) tuberculosis. Besides protecting against TB, BCG vaccination reduces mortality in children because of non-specific cross-protection induced by this vaccine against other unrelated pathogens [12, 13] Initial evidence for this phenomenon was described in Sweden in 1927 by the physician Carl Näslund, who found that during the first year of life, BCGvaccinated newborns had a mortality rate that was three times lower than unvaccinated babies [14]. BCG has been considered as a good vector given its safety shown in vaccinated neonates, children and adults for almost a 100 years and that BCG antigens may act as adjuvants, inducing innate and adaptive immune responses [11, 22,23,24, 44, 45]
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