Improving the vaccine efficacy gap with microbial-derived therapies.

Oral polio and rotavirus vaccines underperform in low-resource settings, a failing linked to distinct microbiome compositions. This Forum examines why empiric probiotics and broad taxonomic approaches are largely ineffective in boosting mucosal vaccine immunity and proposes mechanism-driven microbial therapies that modulate epithelial barriers, utilize immune-modulating metabolites, or mitigate viral interference.