MSTP in PhD Training
Program: Molecular Microbiology and Microbial Pathogenesis
Current advisor: Siyuan Ding, PhD
Undergraduate university: University of Maryland-College Park, 2016
Enrollment year: 2019
Determining the molecular mechanisms that affect rotavirus vaccine efficacy
Rotaviruses (RVs) are the global leading cause of diarrhea-related morbidity and mortality in infants and young children worldwide, causing 128,500 deaths and more than 258 million episodes of diarrhea in 2016. Multiple vaccines have been developed and are currently on the basic pediatric immunization schedule. Yet, RV vaccine efficacy varies across different populations. In a recent meta-analysis, Rotarix vaccine effectiveness in children aged 12-23 months, measured by lab-confirmed RV infection, was 86% in low-mortality countries, compared to 58% in high-mortality countries. This brings us to question, what may be contributing to these discrepancies in vaccine efficacy across different populations? Some contributing factors include differences in microbiome composition, breast milk IgA, environmental force of infection, infection with other gastrointestinal pathogens, nutritional status, circulating RV strains, concomitant polio vaccine administration, and host genetics. We are working to use 3D Matrigel- and 2D monolayer-based donor-derived intestinal enteroids to model the impact of host genetics and microbiome composition on the efficacy of RV vaccines. Unlike the inbred mouse strains, these tractable enteroid models allow us to ask direct questions about viral replication in primary intestinal epithelial cells (IECs), host-RV vaccine strain interactions, and the effect of genetic heterogeneity and microbiota on RV infection.
Antia A, Alvarado DM, Ding S, Ciorba MA. 2022 Adding Fuel to The Fire? A Role of Intraepithelial Lymphocytes in Enteric Immune Responses to SARS-CoV-2 Infection. Gastroenterology, ():S0016-5085(21)04120-2.
Antia A, Pinski AN, Ding S. 2022 Re-Examining Rotavirus Innate Immune Evasion: Potential Applications of the Reverse Genetics System. mBio, ():e0130822.
Anita A, Alvarado DM, Zeng Q, Davis DL, Ciorba M, Ding SA. (2022) SARS-CoV-2 Omicron (BA.1) variant infection of human colon epithelial cells. American Society for Virology (ASV) 2022 Conference, Madison, WI, Abstract.