Jo Frempong

Program: Molecular Genetics and Genomics

Current advisor: Megan T. Baldridge, MD, PhD

Undergraduate university: Trinity College, 2018

Enrollment year: 2021

Research summary
Interrogating mechanism(s) associated with diminished immune responses to oral rotavirus vaccines (RVVs)

My project in the lab of Dr Megan Baldridge focuses on interrogating the mechanism(s) associated with the diminished immune responses to rotavirus vaccines (RVVs) observed in low- and middle-income countries (LMICs) compared to high-income countries.

Rotavirus (RV) is the leading cause of diarrhea-associated morbidity and mortality in children younger than five worldwide. Though RVVs have dramatically reduced global RV hospitalizations and mortality, children in LMICs remain at risk of life-threatening RV disease because vaccine effectiveness in LMICs is significantly lower there than in high-income countries. Multiple contributing factors to differential RVV efficacy have been identified, including breastfeeding and water quality, but their roles have not been fully elucidated.

There is now new appreciation in the field that enteric viral co-infections are associated with the observed diminished immune responses to systemically-administered vaccines. Previous work in the Baldridge laboratory, using virome sequencing of a cohort of Ghanaian infants, suggested a potentially important role for co-infecting non-polio enteroviruses in preventing effective immune responses to oral RVV. Enteroviruses include a wide range of positive-sense single-stranded RNA viruses in the Picornaviridae family and are highly prevalent in infants in LMICs.

We specifically identified Enterovirus B (EV-B) as potentially interfering with development of robust immune responses to oral RVV, but the pathways and mechanisms associated with this interference have not yet been defined. Thus, using ex vivo and in vivo studies in human intestinal organoids (HIOs) and mouse models, I aim to explore enterovirus-RV co-infection as a mechanism by which EV-Bs limit oral RVV replication and immune responses.

Graduate publications