Engineering mRNA-Lipid nanoparticle (LNP) vaccines against multidrug resistant bacteria: current and future prospects

This review highlights the significant potential of mRNA-lipid nanoparticle (LNP) technology for application in bacterial vaccines, with a long-term goal to provide critical tools in controlling problematic microbial infections regardless of their antimicrobial resistance (AMR) profile. The current landscape of bacterial vaccine development, including methods for identification of candidate antigens, are discussed along with emerging design principles for LNP delivery systems. We focus on mRNA-LNP systems for delivery of bacterial vaccine antigens in large part due to their extensive clinical validation, compatibility with reverse vaccinology, and growing prominence in modern vaccinology. Attention is also given to emerging opportunities to develop effective tools to combat severe infections, particularly those caused by AMR bacterial infections. Specific advantages and challenges of RNA-based vaccine platforms and LNP delivery systems compared to other vaccine modalities including strategies are highlighted, with a focus on particular strengths in conserved antigen identification via genome sequencing and recent advances in optimizing LNP composition for induction of strongly protective immunity for vaccine delivery. We argue that mRNA-LNP technology combined with reverse vaccinology approaches has the potential to improve and accelerate bacterial vaccine development, particularly for broadly protective immunity less dependent on bacterial strain surface composition and which are entirely dependent on host immunity, making them agnostic to the issue of antimicrobial resistance.