Loss of Neutrophils and SLPI Reshapes Early Mucosal Inflammatory Responses During Intranasal Vaccination

Vaccines delivered via the nasal route have attracted increasing attention for their capacity to engage the mucosal immune system at the primary site of pathogen entry. However, the early innate mechanisms that shape local immune responses following nasal immunisation remain poorly defined. Here, we identified previously uncharacterised tissue-derived mediators induced during vaccination. Using an intranasally administered whole-cell pertussis (wP) vaccine that recapitulates key features of Bordetella pertussis infection and elicits long-lasting immunity, we show that nasal delivery triggers neutrophil recruitment along with a marked upregulation of secretory leukocyte protease inhibitor (SLPI). Employing SLPI- and neutrophil-deficient mouse models, we demonstrate that SLPI and neutrophils influence the production of key mediators associated with coagulation (PAI-1) and tissue remodelling (MMP-3 and MMP-9) within the airway. Notably, neutrophils also modulate early local total IgA release. Together, these findings suggest a coordinated and context-dependent interplay between cellular and soluble innate components that shape early mucosal immune responses. Furthermore, identified mediators may represent candidate biomarkers in the development of intranasal vaccines against B. pertussis and other pathogens.