Determining the role of micronutrient deficiency in the immune response to oral rotavirus vaccine in a low-resource setting.

About This Grant

The World Health Organization recommends that all children be vaccinated against rotavirus, the most common cause of severe childhood diarrhea and a major cause of morbidity and mortality worldwide. Two oral rotavirus vaccines have proven to be highly efficacious against childhood diarrhea in high- and middle-income countries (85%-98%). However, virtually all trials in sub-Saharan Africa and south Asia have shown lower immune response and much lower vaccine efficacy (40%-64%), leaving many children unprotected. The ultimate goal of this research is to enhance the efficacy of oral vaccines in infants in low-resource settings by identifying the biologic basis for their underperformance in these settings. The research team hypothesizes that the predominant determinants of vaccine failure in low-resource settings are micronutrient deficiencies. Micronutrients, particularly iron, zinc, vitamin A, and vitamin D, play an important role in maintaining the integrity of gut mucosal immunity, a primary site of interaction for oral vaccines, and are critical in activating T and B-cell responses that are essential to oral vaccine response. As a result, key micronutrient deficiencies among mothers in pregnancy may result in a nutrient-deficient fetal environment that handicaps development of a functional infant immune system, while deficiency in infants may also compromise immune development in early live, leaving them unable to mount an effective oral vaccine response. This study will evaluate the associations of four key micronutrients (iron, zinc, vitamin A, and vitamin D) in 250 mother-infant pairs with infants’ failure to develop an effective immune response using plasma samples from a completed randomized, placebo-controlled vaccine efficacy trial in Niger. These four micronutrients were selected for the robust scientific evidence for their critical role in pathways key to oral vaccine efficacy (mucosal immunity and immune cell development) and the relevance to low-resource settings, where deficiency is common. In this study, we aim to test two hypotheses: Aim 1: Low maternal micronutrient concentrations are associated with impaired infant immune response to oral rotavirus vaccine (anti-rotavirus IgA seroconversion at 28 days post-Dose 3). Aim 2: Low micronutrient concentrations in infants are associated with impaired immune response to oral rotavirus vaccine. This study will guide development of new randomized clinical trials (R01) that test the causal effect of micronutrient supplementation on rotavirus vaccine performance. Implementation of such interventions at scale will boost the efficacy of oral vaccines that have historically performed poorly, increasing the impact of immunization programs worldwide.