BCG‐induced protection against Mycobacterium tuberculosis infection: Evidence, mechanisms, and implications for next‐generation vaccines

Abstract

Bacillus Calmette-Guérin (BCG) is a live-attenuated vaccine derived from Mycobacterium bovis of the Mycobacterium tuberculosis (Mtb) complex and was first used in medical practice in 1921. It is administered intradermally after birth, while repeat dosing in adolescence and at other stages of life have been adopted inconsistently in different parts of the world. Efficacy trials have yielded hugely variable results, ranging from 0-80% efficacy against TB disease across different locations. 1 Furthermore, the mechanisms of BCG protection remain poorly understood after 100 years of research and practice, making it difficult to determine what new generation TB vaccines need to induce to provide improved protection.The discovery that BCG protects against Mtb infection (as defined by a positive interferonγ release assay (IGRA) result) and not just progression from Mtb infection to TB disease 2,3 has significant

BCG vaccination induces enhanced frequencies of dendritic cells and altered plasma levels of type I and type III interferons in elderly individuals

“…Bacillus Calmette–Guérin (BCG) is a live-attenuated vaccine largely established to protect against childhood meningitis and disseminated tuberculosis (TB) ( Foster et al, 2021 ) Several epidemiological findings suggest that BCG may increase the capacity of the immune system to fight against pathogens other than TB ( Leentjens et al, 2015 ) and such non-specific responses augment both T cell–mediated adaptive and innate immune memory in a process called trained immunity and this could have important implications for improving vaccination strategies. ( Netea and van Crevel, 2014 ).…”

Molecular and epidemiological characterization of recurrent Mycobacterium ulcerans infections in Benin

“…However, based on findings for other mycobacterial diseases (tuberculosis, leprosy), it is not surprising that primary infection does not enhance immune protection against a second exposure [26,27]. The only vaccine currently available for mycobacterial disease is BCG, which does not provide full protection against M. tuberculosis [28]. Furthermore, studies in a mouse model of M. ulcerans infection showed that mice displaying spontaneous healing after a first infection were not protected against a second challenge with M. ulcerans [29].…”

“…The only vaccine currently available for mycobacterial disease is BCG, which does not provide full protection against M . tuberculosis [ 28 ]. Furthermore, studies in a mouse model of M .…”

Bacteria- and host-derived extracellular vesicles – two sides of the same coin?

“…The function of MycEVs in vivo is less clear. Intra-tracheal administration of EVs released from Mycobacterium bovis BCG, which is an attenuated strain of M. bovis and the only FDA-approved vaccine for Mtb (Foster et al, 2021), leads to an exacerbation of infection when Peptidoglycan (PG) is a polysaccharide made of two glucose derivatives, N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM), that alternate to form long linear chains. The chains are crosslinked to one another by a tetrapeptide -L-alanine, D-glutamine, L-lysine or mesodiaminopimelic acid (DPA), and D-alaninethat extends from the NAM sugar unit, allowing a lattice-like structure to form.…”