Status: Funded - Open
The effects of increased inoculum on oral rotavirus vaccine take and immunogenicity in a low- income country
Benjamin Lee, MD
BACKGROUND: Rotavirus remains the most common cause of diarrheal disease among children and a leading cause of diarrheal death worldwide. Oral rotavirus vaccines are extremely efficacious in high- and middle-income countries, but significantly underperform in low-income countries, including Bangladesh. Two issues frustrate efforts to improve rotavirus vaccine performance: incomplete understanding of the variables impacting vaccine efficacy, and lack of reliable markers of host immune responses to vaccination (immunogenicity) and correlates of protection.
GAP: The effects of vaccine inoculum on vaccine “take,” or the ability of vaccine to exert a biological effect on the host (measured by fecal vaccine shedding or serum antibody seroconversion), and on immunogenicity in low-income countries remain unknown. Further, markers of immunogenicity that show superior performance in low-income countries are needed but are lacking.
HYPOTHESIS: We hypothesize that increasing the inoculum of oral rotavirus vaccine will lead to increased rates of vaccine take and increased immunogenicity, using the standard measure of rotavirus-specific IgA (RV-IgA) seroconversion. In addition, we propose that rotavirus outer capsid antibodies and development of antigenemia or viremia following vaccination have potential as improved markers of immunogenicity over RV-IgA.
METHODS: We will perform a double-blinded, randomized controlled trial to evaluate the effects of high-dose versus standard-dose oral Rotarix (GlaxoSmithKline) on vaccine take and immunogenicity among infants in Dhaka, Bangladesh.
IMPACT: Results from this study may suggest an easily implemented intervention to improve oral rotavirus vaccine performance in low-income countries, preventing morbidity and mortality, and may identify novel immunogenic markers that may be evaluated as correlates of protection.
University of Vermont
United States, Bangladesh