Driving RNA Vaccine Innovation Through Microbiome Insights

Driving RNA vaccine innovation through microbiome insights is an emerging frontier that moves beyond pathogen-only thinking and toward vaccines designed with our resident microbial ecosystems in mind. While RNA vaccine platforms have advanced rapidly in response to major human pathogens, a growing body of work suggests that microbial communities at extra-intestinal sites (including the oral, respiratory, urogenital, and skin microbiomes) can shape baseline immune tone, mucosal barrier function, and inflammatory set points—factors that may ultimately influence vaccine responsiveness, durability, and safety profiles. Positioning microbiome science alongside RNA technology also opens space to explore how microbial signatures can guide vaccine design, stratify recipients, or predict variable responses across different populations and clinical contexts.This topic also invites a broader redefinition of what “successful vaccination” looks like in mucosal and barrier tissues: not only inducing protection against external pathogens, but potentially enabling selective targeting of pathobionts, attenuating harmful inflammation, and supporting tolerance to beneficial commensals. The convergence of RNA delivery systems, synthetic biology, and multi-omics microbiome profiling is setting the stage for next-generation “smart” vaccines—approaches that can be tailored to tissue-specific microbial ecosystems and immune microenvironments, and paired with microbiome-directed interventions (e.g., site-targeted probiotics, prebiotics, postbiotics, or metabolite-based adjuvants) to improve outcomes in vulnerable or dysbiotic cohorts.We welcome articles addressing, but not limited to, the following themes:-Extra-intestinal microbiome determinants of RNA vaccine immunogenicity, reactogenicity, and durability (oral, respiratory, skin, urogenital niches)-Microbiome-informed RNA vaccine antigen selection and design (including targeting pathobionts/opportunists within specific niches)-Mucosal immune programming by resident microbes and implications for intranasal/oral/transdermal RNA vaccine strategies-Multi-omics approaches linking microbial community structure/function to vaccine response heterogeneity (metagenomics, metatranscriptomics, metabolomics, immune profiling)-Microbiome-based biomarkers to predict responders/non-responders or adverse inflammatory outcomes following RNA vaccination-Microbiome–RNA vaccine interactions in early life, aging, pregnancy, and immunocompromised or chronically inflamed populations-Adjunct strategies: probiotics, prebiotics, postbiotics, and niche-targeted microbial metabolites as adjuvants or response modulators alongside RNA vaccines-Effects of antibiotics, antifungals, antivirals, diet, smoking, and environmental exposures on extra-intestinal microbiomes and downstream RNA vaccine performance-Delivery technologies and formulations designed for extra-intestinal sites (nanoparticles, mucosal targeting, tissue-specific uptake) and their interactions with local microbiota-Preclinical models and clinical study designs for establishing causality between extra-intestinal microbiome features and RNA vaccine outcomes-Ethical, regulatory, and translational considerations for microbiome-stratified vaccination and microbiome-modulating co-interventions--Topic Editor Cuncong Zhong is a cofounder of H2Alpha Inc .All other Topic Editors declare no competing interests with regards to the Research Topic subject. Topic editors: Umesh Kalathiya, Cuncong Zhong, Monikaben Padariya Source: https://www.frontiersin.org/research-topics/78162/driving-rna-vaccine-innovation-through-microbiome-insights