Protection against tuberculosis by vaccination of secreted chorismate mutase (Rv1885c) combined with a hepatitis B virus (HBV)-derived peptide, Poly6, and alum adjuvants

Abstract

Tuberculosis (TB) remains a significant global health issue due to the limited efficacy of the Bacillus Calmette-Guérin (BCG) vaccine, highlighting the need for the development of an improved TB vaccine. In this study, we created a novel TB subunit vaccine consisting of TB-secreted chorismate mutase (TBCM) (Rv1885c) and a hepatitis B virus (HBV)-derived peptide (Poly6), which elicits Type I interferon responses, both with and without an alum adjuvant. We evaluated the immunogenicity, protective efficacy, and therapeutic efficacy of this vaccine candidate in an in vivo mouse model. Our results revealed that subcutaneous vaccination with TBCM combined with Poly6 induced stronger antigen-specific humoral and cell-mediated immune responses than TBCM alone or TBCM combined with alum adjuvant. Furthermore, adding the alum adjuvant to TBCM combined with Poly6 significantly enhanced antigen-specific immune responses. Subcutaneous vaccination with TBCM combined with both Poly6 and alum adjuvants effectively protected mice against Mycobacterium tuberculosis (Mtb) K strain infection, demonstrating its potential as a TB vaccine. Additionally, this vaccine platform exhibited therapeutic potential by significantly reducing bacterial loads and lung inflammation in mice previously infected with the virulent Mtb K strain. In conclusion, our findings suggest that TBCM is highly immunogenic in mice and that TBCM combined with both Poly6 and alum adjuvants represents a promising vaccine platform for TB prevention and treatment.

Keywords: A hepatitis B virus (HBV)-derived peptide; Alum adjuvant; Mycobacterium tuberculosis (TB); Poly6; Secreted chorismate mutase (Rv1885c); Vaccine.