Human Nutrition and Oral Vaccine Efficacy

The advent of oral vaccines (OVs) in the mid-twentieth century led to dramatic reductions in the global burden of gut and gut-acquired infectious diseases such as polio, rotavirus, cholera, and typhoid. Paradoxically, OVs have been less effective in low- and middle-income countries (LMICs) where morbidity and mortality from these diseases are highest. This so-called tropical barrier does not reflect intrinsic defects of OV platforms but rather the influence of adverse host and environmental conditions more prevalent in LMIC settings. Among these, nutritional status stands out as a key modifiable determinant of OV performance. The collision of undernutrition and poor sanitation in LMIC contexts fosters repeated exposure to enteropathogens via contaminated food, water, and living environments; proinflammatory gut microbiota; disrupted intestinal mucosal architecture and barrier function; and profoundly altered immune development. Together, these factors hinder the replication and take of OVs. Micronutrient deficiencies—particularly in zinc, vitamin A, vitamin D, and iron—further compromise intestinal epithelial homeostasis, antigen presentation, and antibody responses to undermine OV efficacy. This review synthesizes recent advances in our understanding of how human nutrition shapes OV immunogenicity. By integrating epidemiologic evidence, field interventions, and mechanistic insights, we outline pathways linking diet, gut health, and vaccine response and strategies to close global gaps in OV performance.