Bacillus subtilis Spores as a Vaccine Delivery Platform: A Tool for Resilient Health Defense in Low- and Middle-Income Countries.

The COVID-19 pandemic exposed the urgent need for innovative tools to strengthen pandemic preparedness and health defense, especially in low- and middle-income countries (LMICs). While vaccination has been the cornerstone of the defense strategy against many infectious agents, there is a critical gap in vaccine equity, ensuring it is accessible to all, especially among the most vulnerable populations. The conventional vaccine delivery platforms, through parenteral administration, face notable limitations, including reliance on trained personnel, sterile conditions, and cold chain logistics. The parenteral vaccines often fail to induce robust mucosal immunity, which is critical for preventing infections at mucosal surfaces, the primary entry point for many pathogens. Bacillus subtilis, a Gram-positive, spore-forming bacterium, has emerged as a promising platform for mucosal vaccine delivery owing to its Generally Recognized as Safe (GRAS) status. Its robust spores are highly resilient to harsh environmental conditions, which may eliminate the need for cold chain storage and further facilitate distribution in LMICs. This review explores the potential of B. subtilis as a next-generation vaccine delivery platform, focusing on its unique characteristics, mechanisms of action, and applications in addressing global health challenges. This review also examines existing research demonstrating the safety, immunogenicity, and efficacy of B. subtilis spore-based vaccines while identifying limitations and future directions for optimization as a scalable and adaptable solution for resilient health defense, particularly in LMICs.