Sasirekha Ramani, PhD
Harnessing the Potential of the Microbiome to Improve Rotavirus Vaccine Response
Rotavirus is a leading cause of life-threatening diarrhea and vomiting in children under the age of 5 years. Live, attenuated vaccines to prevent severe rotavirus disease were first licensed in 2006 and are now used in over 100 countries. Since the introduction of vaccines, the number of rotavirus associated deaths has significantly decreased in high-income countries. However, the same vaccines are far less effective in low- and middle-income countries, where millions of diarrheal hospitalizations due to rotavirus continue to occur each year. It is important to develop targeted interventions that will improve the response to rotavirus vaccines in these settings. This project focuses on developing interventions based on gut microbiome of vaccine responders. The intestinal microbiome is an important player in human health and disease. Studies in some low-income countries have shown that the pre-vaccination microbiome of rotavirus vaccine responders is distinct from that of non-responders within the same population. The goal of this project is to identify and test factors produced by “responder bacteria” for their effects on improving rotavirus vaccine response. These evidence-based microbial interventions will first be evaluated for safety and effectiveness in biologically-relevant laboratory model systems. The long-term goal of this work is to translate these microbiome-based interventions into products that can be co-administered with vaccines in order to improve immune responses in children.
I am grateful and honored to have received the PhRMA Foundation Research Starter Grant in Translational Medicine. My laboratory focuses on enteric infections and vaccines, and one of our goals is to improve oral vaccine responses in low- and middle-income countries with high enteric infectious disease burden. This grant helps us establish a pre-clinical pipeline involving organoid cultures and animal models that will allow translation of laboratory findings into interventions that improve child health.