Abstract
A vaccine based on outer membrane vesicles of pertussis (omvPV) is protective in a mouse-challenge model and induces a broad antibody and mixed Th1/Th2/Th17 response against multiple antigens following subcutaneous immunization. However, this route did not result in mucosal immunity and did not prevent nasopharyngeal colonization. In this study, we explored the potential of intranasal immunization with omvPV. Only intranasal immunization induced strong mucosal immune responses that encompasses enhanced pulmonary and nasal IgA antibody levels, mainly directed against Vag8 and LPS. Furthermore, high numbers of IgA- and IgG-producing plasma cells were detected as well as lung-resident IgA memory B-cells. Finally, only intranasal immunization induced pulmonary Th1/Th17-related cytokine responses. The magnitude and type of systemic immunity was comparable between both routes and included high systemic IgG antibody levels, strong IgG-producing plasma cell responses, memory B-cells residing in the spleen and systemic Th1/Th2/Th17-related cytokine responses. Importantly, only intranasal immunization prevented colonization in both the lungs and the nasal cavity. In conclusion, intranasal omvPV immunization induces mucosal IgA and Th17-mediated responses without influencing the systemic immunity profile. These responses resulted in prevention of Bordetella pertussis colonization in the respiratory tract, including the nasal cavity, thereby potentially preventing transmission.
Highlights
A vaccine based on outer membrane vesicles of pertussis is protective in a mouse-challenge model and induces a broad antibody and mixed Th1/Th2/Th17 response against multiple antigens following subcutaneous immunization
We recently showed that omvPV can be administrated directly in the respiratory tract leading to faster bacterial clearance from the lungs compared to subcutaneous immunization[15,21]
The lungs, trachea and nose of naive mice were heavily colonized on day 1 after the B. pertussis challenge and the number of bacteria further increased on day 6 p.c., indicating successful colonization (Fig. 2A–C)
Summary
A vaccine based on outer membrane vesicles of pertussis (omvPV) is protective in a mouse-challenge model and induces a broad antibody and mixed Th1/Th2/Th17 response against multiple antigens following subcutaneous immunization. This route did not result in mucosal immunity and did not prevent nasopharyngeal colonization. Intranasal omvPV immunization induces mucosal IgA and Th17-mediated responses without influencing the systemic immunity profile These responses resulted in prevention of Bordetella pertussis colonization in the respiratory tract, including the nasal cavity, thereby potentially preventing transmission. Pulmonary immunization evoked elevated systemic immunoglobulin G (IgG) antibody levels, IgG-producing plasma cells, memory B-cells, and Th17 cells as compared to subcutaneous immunization. Systemic and mucosal antibody, B-cell and T-cell responses were studied to explore the underlying type of immunity
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