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mRNA vaccines for multidrug-resistant bacteria: promise, challenges, and microbiome-informed strategies
Benjamin Davido1, Paul Loubet2, Azzam Saleh-Mghir3
1Maladies Infectieuses, Hôpital Raymond-Poincaré, Université Paris Saclay, AP-HP, Garches, France; UMR1173, Université Versailles Saint-Quentin, Montigny-Le-Bretonneux, France; Mission Ministérielle de la Prévention des infections et de l'antibiorésistance, Direction Générale de la Santé, Paris, France; SEPSIS Comprehensive Center - IHU SEPSIS, Garches, France.
Abstract:
Antimicrobial resistance (AMR) has made multidrug-resistant organisms (MDROs), particularly ESKAPE-E pathogens (including Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp, and Escherichia coli), a major threat to modern medicine. Although novel antibiotics, antimicrobial stewardship, and infection prevention remain essential, such interventions are unlikely to offset projected AMR trends on their own. Vaccines can help to mitigate AMR by preventing infections and reducing antibiotic exposure. WHO estimates that vaccines targeting 23 pathogens (excluding Neisseria gonorrhoea) could reduce global antibiotic need by 22%, equivalent to 2·5 billion defined daily doses annually. In the mRNA era, modular vaccine platforms enable rapid design of protein antigens and multivalent constructs, with emerging preclinical proof of concept against selected bacterial pathogens. In this Personal View, we argue that mRNA vaccines should be considered enabling platforms for selected protein-based MDRO targets rather than universal solutions for antibacterial vaccine development. We propose a microbiome-informed framework that distinguishes systemic protection from mucosal decolonisation and aligns antigen selection, delivery route, and trial endpoints with colonisation dynamics, microbiome resilience, and AMR reduction goals.
Insights
Messenger RNA (mRNA) vaccines offer a promising avenue to combat antimicrobial resistance (AMR) by targeting multidrug-resistant organisms (MDROs). A strategic, microbiome-informed approach is crucial for developing effective antibacterial vaccines to reduce antibiotic use.
Area of Science:
- Vaccinology and Infectious Disease Research
- Microbiology and Antimicrobial Resistance (AMR)
Background:
- Multidrug-resistant organisms (MDROs), especially ESKAPE pathogens, pose a significant threat to global health.
- Existing interventions like antibiotics and stewardship are insufficient to curb the rising AMR crisis.
- Vaccines present a viable strategy to reduce infections and subsequent antibiotic exposure.
Purpose of the Study:
- To evaluate the potential of mRNA vaccine platforms for developing vaccines against MDROs.
- To propose a framework for designing effective antibacterial vaccines that consider microbiome dynamics.
- To align vaccine strategies with AMR reduction goals.
Main Methods:
- Review of current AMR trends and the role of vaccines in mitigation.
- Exploration of mRNA vaccine technology for rapid antigen design and multivalent constructs.
- Proposal of a microbiome-informed framework for antigen selection, delivery, and trial endpoints.
Main Results:
- WHO estimates suggest vaccines could reduce global antibiotic need by 22%.
- mRNA platforms show preclinical promise for selected bacterial targets.
- A strategic approach is needed, distinguishing systemic protection from mucosal decolonization.
Conclusions:
- mRNA vaccines should be viewed as enabling platforms for specific MDRO targets, not universal antibacterial solutions.
- A microbiome-informed framework is essential for optimizing vaccine efficacy and achieving AMR reduction.
- Integrating colonization dynamics and microbiome resilience into vaccine design is key.
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