Abstract
Mucosal immunity is often required for protection against respiratory pathogens but the underlying cellular and molecular mechanisms of induction remain poorly understood. Here, systems vaccinology was used to identify immune signatures after pulmonary or subcutaneous immunization of mice with pertussis outer membrane vesicles. Pulmonary immunization led to improved protection, exclusively induced mucosal immunoglobulin A (IgA) and T helper type 17 (Th17) responses, and in addition evoked elevated systemic immunoglobulin G (IgG) antibody levels, IgG-producing plasma cells, memory B cells, and Th17 cells. These adaptive responses were preceded by unique local expression of genes of the innate immune response related to Th17 (e.g., Rorc) and IgA responses (e.g., Pigr) in addition to local and systemic secretion of Th1/Th17-promoting cytokines. This comprehensive systems approach identifies the effect of the administration route on the development of mucosal immunity, its importance in protection against Bordetella pertussis, and reveals potential molecular correlates of vaccine immunity to this reemerging pathogen.
Highlights
Optimal protection against respiratory pathogens requires induction of mucosal immunity in the lungs, where tissueresident memory T cells[1,2] and immunoglobulin A (IgA) antibodies[3] play a pivotal role in the rapid recognition of pathogens
Acellular pertussis vaccine induces a systemic immune response characterized by the formation of immunoglobulin G (IgG) antibodies and a T helper type 2 (Th2)-dominated response,[6,7,8,9] whereas a Th1/Th17 response is preferable for protection against infection.[8]
A dose-dependent immunization study comparing 1 and 10 mg outer membrane vesicle pertussis vaccine (omvPV) demonstrated that administration of 10 mg omvPV resulted in complete lung clearance of pulmonary immunized mice (PM mice) and most of subcutaneously immunized mice (SC mice) 3 days after challenge. (Supplementary Figure S1)
Summary
Optimal protection against respiratory pathogens requires induction of mucosal immunity in the lungs, where tissueresident memory T cells[1,2] and immunoglobulin A (IgA) antibodies[3] play a pivotal role in the rapid recognition of pathogens. Induction of these responses by immunization is appealing. Current vaccines against respiratory pathogens, including Bordetella pertussis, which causes whooping cough, do not induce mucosal immunity. Improvement of pertussis vaccines and optimized vaccination strategies[4,5] are required, as whooping cough persists as an endemic disease even in highly vaccinated populations. This response is comparable to the response induced by a B. pertussis infection, but importantly lacks the mucosal immune responses.[8,12,13,14]
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