MINI REVIEW article
Front. Immunol.
Sec. Vaccines and Molecular Therapeutics
This article is part of the Research TopicInnovative Immunological Strategies for Overcoming Antimicrobial Resistance and Enhancing Vaccine DevelopmentView all 10 articles
Next-Generation Vaccines Against Bacterial Pathogens: mRNA and Beyond
Provisionally accepted
- 1The Second Hospital of Jilin University, Changchun, China
- 2First Affiliated Hospital of Jilin University, Changchun, China
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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.
Keywords: mRNA vaccines, antimicrobial resistance, ESKAPE pathogens, Tuberculosis, DNA Vaccines, nanoparticle
Received: 21 Sep 2025; Accepted: 13 Nov 2025.
Copyright: © 2025 Chen, Gu, Song and Si. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Lihui Si, silihuidoctor@jlu.edu.cn
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