Project Details

Identification of adjuvants through human in vitro modeling for infant antiviral vaccine development

Sanya Thomas, MD, MPH, MMSc

Summary

BACKGROUND: Infants are highly susceptible to influenza infection, a leading cause of early-life hospitalization, yet no influenza vaccines are approved for use in infants under six months of age, making maternal immunization a critical strategy for protection during this vulnerable period. However, maternal antibodies may attenuate infant vaccine responses, underscoring the need to better understand maternal-infant immune interactions and develop vaccine approaches that enhance robust, virus-specific early-life immunity. GAP: Influence of maternal-infant immune interplay on the development of infant antiviral T-cell immunity remains incompletely defined, and robust pre-clinical data identifying optimal adjuvants for infant influenza vaccines are lacking. Addressing these gaps is critical for the rational design of safe and effective antiviral vaccines for infants. HYPOTHESIS: Infants of vaccinated mothers exhibit a basal tolerogenic T-cell phenotype which can be re-directed toward a virus-specific Th1 and CD8+ T-cell response with adjuvantation. METHODS: I will obtain blood samples of 15 mother-baby dyads from Massachusetts General Hospital to perform baseline immune profiling and assess virus-specific cellular immunity following stimulation of mononuclear cells with novel adjuvants targeting pattern recognition receptors. Immune responses will be characterized using flow cytometry, cytokine and chemokine profiling, and single-cell RNA-sequencing, with integrated multi-omic analyses to define immune signatures associated with adjuvant-driven modulation of infant immunity. RESULTS: Pending. IMPACT: This work will advance rational vaccine design by identifying adjuvant combinations that enhance virus-specific cellular immunity in infants. The methodological framework can be applied to other high-burden pediatric pathogens, broadly contributing to child health and global vaccine development. Website Link: https://research.childrenshospital.org/research-units/pediatrics-research/precision-vaccines-program