Robust immune responses to intranasal vaccine targeting Bordetella pertussis antigens to claudin-4 on mucosal...

Despite high global vaccination rates, pertussis remains uncontrolled and is increasing in many regions. The present study aimed to develop an intranasal (I.N.) vaccine (F1S1-C-CPE) against Bordetella (B.) pertussis. This vaccine comprises the C-terminal fragment of Clostridium perfringens enterotoxin (C-CPE) fused with F1S1 antigen, which consists of the S1 subunit of pertussis toxin and the immunodominant domain of filamentous hemagglutinin (F1). C-CPE specifically targets Claudin-4 on mucosal microfold cells, which enhances immune response at the site of infection. We evaluated the immunogenicity and protective efficacy of this construct following I.N. immunization in BALB/c mice. Significant differences in serum IgG and IgA, as well as lung IgA levels were observed among mice immunized with F1S1, CPE + F1S1, F1S1-C-CPE, and PBS (p < 0.0001). Notably, the F1S1-C-CPE group exhibited significantly higher levels of IgA in both serum and lung extracts compared to the F1S1 or CPE + F1S1 groups (p < 0.05). Moreover, analysis of cell-mediated responses indicated that IFN-γ and IL-17 levels were highest in group F1S1-C-CPE, significantly exceeding those in the F1S1, F1S1+C-CPE groups (p < 0.001). Cytokine profile analysis in lung tissue post-challenge indicated the greatest fold increases in mRNA levels of IFN-γ, IL-6, IL-17, and IL-10 in group F1S1-C-CPE (p < 0.0001). The challenge results indicated that I.N. immunization with F1S1-C-CPE protein effectively controls B. pertussis infection (p < 0.0001). The results indicate the development of mucosal and systemic humoral and Th1/Th17 responses, which are critical in controlling infection. Overall, our findings highlight the potential of the F1S1-C-CPE I.N. vaccine as a powerful tool in combating pertussis.