Active and passive humoral immunity to enteric adenovirus infection in Bangladeshi children

PROJECT SUMMARY/ABSTRACT Candidate: I am an Assistant Professor at the University of Virginia (UVA) in the Division of Infectious Disease and International Health and a KL2- Funded Scholar in the Integrated Translational Health Research Institute of Virginia (iTHRIV) Scholars Program. I have pursued research in host pathogen immune interactions with Dr. William Petri for the past 6 years. Beginning initially with enteric pathogens and shifting to SARS-CoV-2 during the pandemic, I will now return to my work in diarrheal disease utilizing my background in viral immunology through study of adenovirus (AdV) 40/41 infection, a major cause of childhood diarrheal illness in low- and middle- income countries (LMIC). Career Development Plan/Career Goals & Objectives: My goal is to become an independent translational investigator. I will do so by furthering my knowledge base in the design of clinical trials, host pathogen immune interactions, viral immunology and data analysis. I will utilize my advisory committee who are not only successfully funded researchers but have a proven track record for mentoring young physician scientists. Research Plan: Characterize the systemic and mucosal immune response to AdV 40/41 infection in children in Bangladesh and determine the efficacy breast milk antibodies in providing passive immunity. Aim 1 (PASSIVE IMMUNITY): (1A) Describe the antibody repertoire to AdV 40/41 in the breast milk of mothers of Bangladeshi children using a novel protein microarray and (1B) determine their association with infection in the first 2 years of life. Plan: Determine maternal breast milk antibody breadth and magnitude, and test for its association to infant infection. Aim 2 (ACTIVE IMMUNITY): Characterize the antibody responses to AdV 40/41 infection in Bangladeshi children and test for their association with subsequent infection utilizing longitudinal (2A) serum and (2B) stool samples. Plan: Describe mucosal and systemic antibody scope and magnitude and test for association with protection from subsequent infection. Mentor/Co-Mentor(s), and Collaborator(s): The primary mentor of this K23, Dr. Petri, has a 30-year record of NIH Funding and has mentored 10 prior K awardees, 6 of whom have already made the K to R transition. My mentors include experts in immunology, virology, childhood diarrheal disease and statistics. Environment and Institutional Commitment to the Candidate: The intellectual environment at UVA is robust. I have a strong commitment from my Department and Division assuring 90% protected research time regardless of the outcome of this K23 proposal, and support of my continued mentorship under Dr. Petri at UVA.