Abstract
Influenza remains a global health threat, causing significant morbidity and mortality due to its high transmissibility
and capacity to evolve through antigenic drift. Although current seasonal vaccines reduce disease burden, their
effectiveness can be compromised by continual viral evolution. A key challenge lies in understanding the interplay
between systemic and mucosal immunity-specially how immunological imprinting shapes responses to novel
strains. To address these gaps, this research integrates three unique resources. First, Controlled Human Infection
Models (CHIMs) at Vaccinopolis in Antwerp allow precise control over influenza strain, dose, and timing of
infection. This design provides an unprecedented opportunity to dissect the mechanisms of mucosal immunity, viral
shedding, and the interplay between naïve and memory responses. Second, infant cohort samples from ongoing
studies in Rome and Antwerp offer insights into how early-life exposures imprint immune memory. Third, by
leveraging dyadic (mother-infant) samples from prior maternal vaccination studies, we can track the
intergenerational transmission of immunity and investigate how maternal antibodies shape infant immune
ontogeny. Using a systems biology approach, the project will characterize immune responses at the gene, protein,
and cellular levels. We will perform multi-omics analyses (e.g., transcriptomics, proteomics) to identify immune
correlates of protection, focusing on mucosal sites-the initial interface for infection and transmission. By combining
adult CHIM data with longitudinal infant cohort and maternal-infant dyad findings, this research seeks to elucidate
influenza immunity both mucosal and systemic responses, and how targeted interventions (e.g., novel adjuvants,
vaccine formulations) might overcome existing immune barriers.
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