Jongchan Kim, AUMC

Jongchan Kim1, Charlie C Luchen1,2, Megan T Baldridge3, Sasirekha Ramani4, Adithya Sridhar5,6, Katja Wolthers5, Vanessa C Harris1  1 Department of Global Health (AIGHD), Amsterdam University Medical Center, Academic Medical Center, Amsterdam, the Netherlands; 2 Enteric Disease and Vaccine Research Unit, Center for Infectious Disease Research in Zambia, Lusaka, Zambia; 3 Division of Infectious Diseases, Department of Medicine, Edison Family Center for Genome Sciences & Systems Biology, Washington University School of Medicine, St. Louis, MO, USA; 4 Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA; 5 OrganoVIR Labs, Department of Medical Microbiology, Amsterdam University Medical Center, Amsterdam, the Netherlands; 6 Emma Children’s Hospital, Department of Pediatric Infectious Diseases, Amsterdam University Medical Center, The Netherlands

Vaccines

Rotavirus remains a major contributor to pediatric mortality, responsible for over 200,000 deaths annually, with the highest burden observed in low- and middle-income countries (LMICs). While the rotavirus vaccine (RVV) has significantly reduced the global burden of rotavirus in high-income countries, its effectiveness remains markedly attenuated within LMICs. Despite being the most effective intervention, the reduced vaccine performance in LMICs has prompted further investigations into potential underlying causes. Recent studies suggest asymptomatic enteric viral co-infections associated with negative seroconversion in LMICs, potentially confounding vaccine-induced immune response. This study seeks to explicate viral-viral interactions that contribute to poor vaccine performance by analyzing the enteric virome and host immune responses at critical RVV administration periods (6-8, 10, and 14 weeks of age) in Zambian and Ghanaian infants. The enteric virome will be characterized through shotgun metagenomic sequencing, enabling the unbiased assessment of viral communities. In parallel, host immune responses will be quantified through cytokine profiling using multiplex assays, with a focus on cytokines identified as playing a role in RV replication. We will use multivariate analysis to examine how different viral communities and immune markers relate to clinical RV gastroenteritis outcomes, providing insight into the virus-virus and virus-host interactions affecting vaccine effectiveness. Building on these findings, future investigations utilizing relevant ex vivo models, notably human intestinal organoids, will enable exploring rotavirus-enterovirus-host interactions. By combining detailed virome characterization, immune response profiling, and mechanistic studies, this research aims to inform targeted strategies for improving RVV efficacy, especially in LMICs where vaccine performance remains suboptimal.