Name
Modulation of Oral Rotavirus Vaccine Replication in Infants by the Intestinal Microbiome
Presenter
Lakshmi Somasundaram, Baylor College of Medicine
Co-Author(s)
Lakshmi N. Somasundaram (1), Jaelyn M. Simmons (1), José O. Cantu (1), Ken Dickson (1), Eva C. Preisner (1), Laura Schaefer (1), Khuzwayo C. Jere (2,3), Vanessa C. Harris (4,5), Andrew T. Gewirtz (6), Robert A. Britton (1), Sasirekha Ramani (1)
1. Baylor College of Medicine, Houston, TX, USA
2. Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, University of Malawi, Blantyre, Malawi
3. Institute of Infection and Global Health, University of Liverpool, Liverpool, UK
4. Department of Global Health, Amsterdam Institute for Global Health and Development (AIGHD), Amsterdam University Medical Centers, University of Amsterdam, The Netherlands
5. Division of Infectious Diseases, Department of Internal Medicine, Amsterdam University Medical Centers, University of Amsterdam, The Netherlands
6. Georgia State University (GSU), Atlanta, GA, USA
Abstract Category
Vaccines
Abstract
The effectiveness of live attenuated oral rotavirus vaccines (ORVs) is poor in many low- and lower-middle income countries where rotavirus disease burden is high. Differences in infant gut microbiome composition have been associated with differences in infant ORV response, but mechanisms to explain these associations have not been established. We aim to understand how the gut microbiome impacts infant ORV replication using infant human intestinal enteroids (HIEs) with an overall goal of identifying interventions to improve ORV response.
Fecal microbiome transplant studies from vaccine responder and non-responder infants have shown that Clostridium perfringens reduced murine RV replication and seroresponse in germ-free mice. Population studies have described associations between the presence of Proteobacteria and seroconversion to ORV. To determine the effects of C. perfringens and candidate Proteobacteria on ORV replication, we treated infant HIEs with either bacterial supernatants or inactivated bacteria for 24 hours prior to infection with an ORV. While pretreatment of infant HIEs with C. perfringens supernatants had no effect on ORV replication, inactivated C. perfringens reduced replication by modulating epithelial interferon response. In contrast, specific proteobacteria supernatants significantly enhanced ORV replication. In addition to these specific candidate bacteria, we are evaluating the effect of complex microbial communities on ORV replication through cultivation of stool samples from ORV responder and non-responder infants in mini-bioreactor arrays.
Defining how the microbiome modulates ORV replication will be important in designing effective interventions to improve infant health outcomes within populations with low ORV effectiveness.
Fecal microbiome transplant studies from vaccine responder and non-responder infants have shown that Clostridium perfringens reduced murine RV replication and seroresponse in germ-free mice. Population studies have described associations between the presence of Proteobacteria and seroconversion to ORV. To determine the effects of C. perfringens and candidate Proteobacteria on ORV replication, we treated infant HIEs with either bacterial supernatants or inactivated bacteria for 24 hours prior to infection with an ORV. While pretreatment of infant HIEs with C. perfringens supernatants had no effect on ORV replication, inactivated C. perfringens reduced replication by modulating epithelial interferon response. In contrast, specific proteobacteria supernatants significantly enhanced ORV replication. In addition to these specific candidate bacteria, we are evaluating the effect of complex microbial communities on ORV replication through cultivation of stool samples from ORV responder and non-responder infants in mini-bioreactor arrays.
Defining how the microbiome modulates ORV replication will be important in designing effective interventions to improve infant health outcomes within populations with low ORV effectiveness.