Booster vaccine reduces BCG-primed mice's protection against primary Mycobacterium tuberculosis infection by raising IL-10 levels.

BACKGROUND

Around 90% of global tuberculosis (TB) new cases occur in adolescents and adults. The BCG vaccine, which is widely administered to infants, is inadequate for adult protection, underscoring the necessity for developing an effective booster vaccine for adult TB prevention. However, the effectiveness of these booster vaccines, especially against primary Mycobacterium tuberculosis (M.tb) infection, remains contentious, and their underlying mechanisms are not fully understood. Emerging evidence, including our previous findings, suggests that interleukin-10 (IL-10)-mediated immune regulation may influence T cell responses following booster immunization and potentially contribute to the limited efficacy observed in preventing primary M.tb infection, although this remains to be further clarified.

METHODS

This study evaluated subunit vaccines incorporating different M.tb antigens (A1D4 or CMFO) and adjuvants (DMT or DT) as booster interventions in mice previously primed with BCG. qRT-PCR was employed to assess IL-10 mRNA levels, FACS and ICS were used to detect IL-10 positive cell populations in lymph nodes, spleen, and lungs one to three weeks following the booster administration. Additionally, the effects of inhibiting IL-10 receptor signaling using a monoclonal antibody (mAb) on T cell responses and the protective efficacy against aerosolized M.tb infection were further explored.

RESULTS

The administration of the same adjuvant DMT in combination with different recombinant antigens A1D4 and CMFO, or with a different adjuvant, DT, to formulate CMFO/DT as booster vaccines in BCG-primed mice, led to an increase in IL-10 levels in the lymph nodes, spleen, and lungs within three weeks. This occurred despite variations in expression levels, expression sites, and expression timings. Specifically, only modest increases in IL-10 levels were observed in the DMT-adjuvanted groups, whereas a more pronounced elevation was detected in the DT-adjuvanted group. This increase in IL-10 was primarily attributed to its expression by T and Th cells in the lungs. Blocking IL-10 signaling using mAb enhanced the resistance of mice, which had received the BCG prime-CMFO/DT boost, against aerosol infection with 300 CFU of M.tb. This enhancement was achieved by increasing the presence of antigen-specific and memory CD4+ T cells in the lungs.

CONCLUSION

The adjuvant and antigen composition of the booster vaccine influenced IL-10 expression following BCG priming. While IL-10 induction was relatively modest in the DMT-adjuvanted groups and was not associated with a marked change in protective efficacy, elevated IL-10 levels in the DT-adjuvanted group were accompanied by improved protection upon IL-10 blockade. These results indicate that IL-10 may contribute to the modulation of vaccine-induced immunity in a context-dependent manner. Thus, IL-10 has the potential to serve as an auxiliary biomarker for the preliminary assessment of booster vaccine performance, although its utility requires further validation.