Rotavirus is a major contributor to childhood diarrhea and mortality worldwide. Though rotavirus vaccines have made this pathogen less of a threat in the developed world, vaccination is less effective in developing countries for unknown reasons. Recent work highlighted specific bacteria of the intestinal microbiome that correlate with response or nonresponse to rotavirus vaccination in human infants, indicating an important contribution of the microbiome to development of immunity. Thorough characterization of specific functional differences in the microbiome that correlate with immunity is critical to identifying therapeutic targets. Further, testing a variety of interventions, using a well-established mouse rotavirus model, to target these communities will identify practical means to enhance rotavirus vaccine responses in children.
· Develop “humanized” vaccine nonresponder and responder mice for intervention testing.
· Determine the effects of targeted antimicrobials on rotavirus infection.
· Define the contribution of specific bacterial taxa and products to rotavirus immunity.
Potential impact on child health
Protecting children in developing countries from potentially deadly infection by rotavirus is a key issue for global pediatric health. Defining specific interventions to modulate the microbiome for optimal vaccine responsiveness will be critically important to reducing the worldwide burden of rotavirus.