Pharmaceutical design of mRNA vaccines for endemic infectious diseases: integrating antigen discovery with platform engineering

Endemic infections and enteric pathogens, among others, persist largely because of their untreatable nature outside the protection afforded by prior exposure, and, to a greater extent, denote control rather than elimination. New developments in antigen identification, structural vaccinology, and systems immunology make it now possible to rationally identify and optimize protective epitopes with a level of confidence that was not possible before. Meanwhile, technological advances in mRNA platform engineering have also promoted the development of scalable, programmable vaccines that can be rapidly modified, cost-effective, and expanded across diverse pathogen landscapes. Here, we provide an overview of progress at the intersection of antigen design and pharmaceutical formulation, exemplifying how sequence engineering, codon optimization, nucleoside modification, and optimized lipid nanoparticle delivery systems contribute to defining the potency, safety, and thermostability of mRNA vaccines. New leading candidates for regionally endemic pathogens are discussed with a focus on matching the immunogen to population-level genetic diversity of hosts, variable antigenicity, and epidemiological patterns. These advancements demonstrate that combining precision antigen identification with mRNA platform technologies may enable rapid development of vaccines appropriate for diseases endemic in relevant settings. Ongoing advancement depends on aligning scientific novelty with manufacturability, access for all, and region-specific public health priorities.