Project Details

Human in vitro modeling of the infant nasal mucosa and assessment of pneumococcal vaccine adjuvants

Colleen Sedney, PhD

Summary

BACKGROUND: Pneumonia remains the leading cause of infection-associated deaths in children under the age of 5 despite the widespread use of intramuscularly administered Pneumococcal Conjugate vaccines (PCVs). GAP: Numerous murine in vivo studies suggest that improved formulation of vaccines for protection at the site of transmission/infection could lead to enhanced protection. The use of human in vitro modeling can meet the unmet need for safe and reliable models to test the efficacy of mucosal PCV adjuvants in children. HYPOTHESIS: I hypothesize that utilization of multiplatform modeling of the human immune system will identify vaccine formulations suitable for protecting children against Streptococcus pneumoniae at mucosal sites. METHODS: Nasal epithelial cells (NECs) from children between the ages of 2-5 (n=8) and adults aged 18-45 (n=8) will be cultured at air-liquid interface and donor-matched monocyte-derived dendritic cells (moDCs) be co-cultured in the basal compartment. Various pneumococcal adjuvants will be applied to the NECs and the ability of adjuvants to penetrate the epithelial layer and activate the underlying moDCs will be assessed via multi-OMICS and data integration. RESULTS: Pending. IMPACT: As one of the leading causes for childhood hospitalization and death, safe, effective, and targeted vaccines for children against Sp must be urgently developed. The novel combination of primary nasal ALI cultures with our well-established blood-based human in vitro platform will allow for assessment of mucosal PCV vaccine adjuvants, which can directly influence potential vaccine targets. Website Link: https://research.childrenshospital.org/research-units/pediatrics-research/precision-vaccines-program