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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.

The Lancet. Microbe
|July 22, 2026
PubMed

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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