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Published on: August 17, 2022
Next-generation vaccines against bacterial pathogens: mRNA and beyond
Huimin Chen1, Ye Gu1, Lei Song2
1Department of Pediatric Surgery, The Second Hospital of Jilin University, Changchun, China.
Abstract:
The global rise of multidrug-resistant (MDR) bacterial infections has exacerbated the need for effective vaccines to prevent these hard-to-treat pathogens. Traditional vaccine approaches have achieved tremendous successes but often fall short for pathogens like Mycobacterium tuberculosis (TB), which evades host immunity through complex mechanisms, and for multidrug-resistant ESKAPE bacteria, where antibiotic resistance and antigenic variability complicate effective vaccine development. The COVID-19 pandemic spurred unprecedented advances in vaccine technology - particularly mRNA vaccines - reviving interest in novel platforms for bacterial diseases. Here we review next-generation vaccine strategies, focusing on nucleic acid-based platforms such as mRNA, DNA, and self-amplifying RNA (saRNA), as well as viral vector vaccines. We also examine nanoparticle technologies that serve as delivery systems or adjuvant platforms across these approaches. We discuss the unique opportunities of mRNA vaccines to induce both robust antibody and T-cell responses required for intracellular infections like TB, as well as the challenges of antigen discovery and delivery (e.g. lipid nanoparticles). Each platform's mechanism, immunogenic profile, current development status, and challenges are analyzed, including comparative insights. We highlight recent progress such as mRNA vaccine candidates against TB entering clinical trials and saRNA prototypes protecting against plague in animals. Finally, we provide a perspective on the future of vaccine strategies to combat antimicrobial resistance (AMR) - emphasizing the integration of multiple platforms, global collaborative efforts, regulatory pathways, and the translational hurdles that must be overcome to bring these next-generation vaccines from bench to bedside.
Insights
Next-generation vaccines, including mRNA and nucleic acid-based platforms, show promise for combating multidrug-resistant bacterial infections like tuberculosis (TB) and ESKAPE pathogens. These advanced strategies aim to overcome challenges in traditional vaccine development against complex bacteria.
Area of Science:
- * Infectious Diseases and Vaccinology
- * Microbiology and Immunology
Background:
- * Rising global prevalence of multidrug-resistant (MDR) bacterial infections necessitates novel prevention strategies.
- * Traditional vaccines face challenges against pathogens like *Mycobacterium tuberculosis* (TB) and ESKAPE bacteria due to complex immune evasion and antigenic variability.
- * Advances in vaccine technology, particularly mRNA platforms spurred by the COVID-19 pandemic, offer new hope for bacterial diseases.
Purpose of the Study:
- * To review next-generation vaccine strategies for combating MDR bacterial infections.
- * To analyze nucleic acid-based platforms (mRNA, DNA, saRNA) and viral vector vaccines.
- * To examine nanoparticle delivery systems and adjuvant platforms in vaccine development.
Main Methods:
- * Comprehensive literature review of current and emerging vaccine platforms.
- * Analysis of mRNA, DNA, saRNA, and viral vector vaccine mechanisms and immunogenicity.
- * Evaluation of nanoparticle technologies for vaccine delivery and adjuvant applications.
- * Comparative assessment of platform status, challenges, and progress.
Main Results:
- * mRNA vaccines offer potential for robust antibody and T-cell responses against intracellular pathogens like TB.
- * Nucleic acid-based vaccines (mRNA, saRNA) and viral vectors are being explored for bacterial targets.
- * Nanoparticle technologies are crucial for delivery and enhancing immune responses.
- * Early-stage successes include mRNA TB vaccine candidates in clinical trials and saRNA plague vaccines in animal models.
Conclusions:
- * Next-generation vaccine platforms hold significant potential to address the threat of antimicrobial resistance (AMR).
- * Overcoming challenges in antigen discovery, delivery, and clinical translation is critical for success.
- * Integration of multiple platforms and global collaboration are essential for developing effective vaccines against MDR bacteria.
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