rBCG::PUMA exhibits enhanced immunogenicity compared to BCG in mice

Area of Science:

• Immunology
• Vaccinology
• Microbiology

Background:

• Tuberculosis (TB) remains a significant global health challenge.
• Current Bacillus Calmette-Guérin (BCG) vaccine shows limited efficacy against adult pulmonary TB.
• There is a critical need for novel and improved TB vaccine strategies.

Purpose of the Study:

• To engineer a recombinant BCG strain, rBCG::PUMA, expressing the pro-apoptotic gene PUMA.
• To evaluate the immunogenicity and safety of rBCG::PUMA in mouse models.
• To explore the potential of apoptosis-targeted vaccine design for TB.

Main Methods:

• Engineering of a recombinant BCG strain (rBCG::PUMA) expressing the PUMA gene.
• In vitro assessment of macrophage apoptosis.
• In vivo analysis of cellular and humoral immune responses in mouse models.
• Evaluation of safety profile compared to parental BCG.

Main Results:

• rBCG::PUMA significantly increased macrophage apoptosis in vitro.
• Enhanced Th1-biased immune response with elevated IFN-γ, TNF-α, IL-2, and IL-12p70.
• Increased CD8+ central memory T cells and CD4+ effector memory T cells.
• Stronger humoral responses, including increased PPD-specific IgG antibodies.
• Comparable safety profile to the parental BCG strain.

Conclusions:

• Enhancing the apoptotic pathway via PUMA expression broadens and boosts BCG immunogenicity.
• rBCG::PUMA demonstrates improved cellular and humoral immunity, memory T cell generation, and macrophage activity.
• The vaccine platform maintains a favorable safety profile.
• Further evaluation in a Mycobacterium tuberculosis challenge model is required to determine protective efficacy.