Bacterial mRNA Vaccines: Programming Immunity Against Antimicrobial Resistance

The relentless rise of antimicrobial resistance poses a critical threat to global health, urgently demanding the development of antibacterial vaccines. Messenger RNA (mRNA) technology, validated during the COVID-19 pandemic, offers a powerful platform of fast development and flexibility. However, its application against bacterial pathogens remains an emerging frontier due to the structural complexity of bacterial antigens, challenges in achieving effective mucosal and cellular delivery, and the need to elicit balanced Th1/Th17-dominated immune responses for durable protection. Progress in antigen design, mRNA engineering, and lipid nanoparticle (LNP) delivery has enabled early preclinical success against Mycobacterium tuberculosis, Pseudomonas aeruginosa, and Streptococcus pneumoniae. Yet, challenges such as complex antigen expression, mucosal targeting, and immune durability persist. This review provides a brief overview of recent advances in bacterial mRNA vaccine design, including antigen selection, mRNA engineering, and delivery platform optimization. Additionally, we summarize current preclinical progress across key bacterial pathogens and highlight emerging strategies that integrate AI-guided antigen discovery, synthetic biology, and next-generation delivery systems to accelerate clinical translation. Finally, we highlight the prospects of bacterial mRNA vaccines by integrating synthetic biology, AI-driven antigen prediction, and advanced delivery systems. These cutting-edge technologies hold the promise of overcoming existing barriers, ultimately establishing mRNA vaccines as a viable and powerful strategy to curb the tide of antibiotic-resistant infections.