Does mucosal BCG vaccination induce “protective” immunity ?

Vaccine-induced protection against Mtb infection and tB is dependent on mycobacteria- specific immune responses at the site of infection. (Source Scriba & Nemes, 2019)

Vaccine-induced protection against Mtb infection and tuberculosis is dependent on mycobacteria- specific immune responses at the site of infection. (Source Scriba & Nemes, 2019)

One of the suggested pitfalls of intradermal (id-) BCG vaccination is the inability to induce robust mucosal immunity. Researchers hypothesise that BCG vaccination at the site of infection (lung mucosal (muc-)) may overcome this pitfall by inducing robust mucosal immunity. Researchers from Netherlands aimed to determine the kinetics and effect of either id- and lung muc-BCG vaccination against repeated low dose Mycobacterium tuberculosis (Mtb) challenge.

Both id- and muc- BCG vaccination induced Mycobacterial-specific CD4+ T cell responses. Upon Mtb low dose challenge, muc-BCG vaccination significantly delayed induction of M.tb-specific IFN-γ producing CD4 T cells compared to id-BCG vaccination. This finding was illustrated by both slower IFN-γ release assay conversion rates and lower levels of CFP10-ESAT6-specificIFN-γ producing CD4 T cells post conversion. Additionally, muc-BCG vaccinated macaques exhibited lower lung and lymph node inflammation and pathology, as well as lower bacterial load. Interestingly 8 weeks into the Mtb infection phase, none of the muc-BCG vaccinated macaques had detectable bacterial load in bronchoalveolar lavage fluid (BALF). This suggests muc-BCG vaccination induced lung mucosal immunity prevents establishment of sustained Mtb infection.

Polyfunctional profiles in responses to viral infections are synonymous with increased T cell mediated protection. Whether this is also true for mycobacterial immunity has not been determined. muc-BCG vaccination induced higher proportions of lung mucosal Th1 and Th17 cytokine producing CD4+ T cells than id-BCG vaccination. Surprisingly, induction of IL-17 and Il-10 was only observed in response to muc-BCG vaccination but not id-BCG vaccination nor M.tb challenge. Interestingly, no difference was observed between muc- and id-BCG vaccination induced systemic immunity.

In summary Dijkman et al., identified Il-17A and IL-10 production by CD4+ T cells in BALF as a potential correlate of protection. Where as Th1 CD4+ T cells predominantly after Mtb challenge were associated with tuberculosis disease and a potential correlate of disease progression.

Journal Article: Dijkman et al., 2019. Prevention of tuberculosis infection and disease by local BCG in repeatedly exposed rhesus macaques. Nature Medicine.


Article by Cheleka AM Mpande

International Union of Immunological SocietiesUniversity of South AfricaInstitute of Infectious Disease and Molecular MedicineScience Education PrizesElizabeth Glazer Pediatric Aids Foundation