Fig 1.
Proposed model of protective immunity to primary infection with Bordetella pertussis in the respiratory tract.
A) Infiltrating and resident immune cells and molecules that control infection (based on studies in mouse models). Inhaled B. pertussis (Bp) binds to respiratory epithelial cells. Resident dendritic cells (DC) and alveolar macrophages (MΦ) sense the bacteria, secrete T cell polarizing cytokines and present antigens to naïve T cells (in the local lymph nodes), which differentiate into Th1 and Th17 cells (also into Treg cells that regulate immune responses and inflammation). γδ T cells and NK cells produce early IL-17 and IFN-γ, whereas Th1 and Th17 produce sustained IFN-γ and IL-17, respectively. IL-17 promotes production of AMPs, which have direct bactericidal activity, and CXCL1 and CXCL2 by epithelial cells, which recruit and activate neutrophils that phagocytose and kill B. pertussis. IFN-γ activates macrophages, which phagocytose and kill B. pertussis. Uptake of B. pertussis by macrophages is enhanced by B. pertussis-specific antibodies (IgG and IgA). Antibodies also neutralize B. pertussis toxins. Infiltrating Th1 and Th17 cells become resident TRM cells that persist in the respiratory tract poised to respond rapidly to re-infection. B) Immune effector cells and modules that mediate protective immunity against B. pertussis infection of the respiratory tract. Created in BioRender. Mills, K. (2026) https://BioRender.com/x9wlb9l.
Table 1.
Vaccine induced immunity to Bordetella pertussis.
Fig 2.
Immunity induced with parenterally-delivered aP vaccines versus next-generation mucosal pertussis vaccines.
Parenteral immunization with current aP vaccines induces circulating IgG,Th2 and Treg cells, and prevents pertussis disease (through antibody-mediated neutralization of Bordetella pertussis toxins). However, aP vaccines do not induce mucosal antibodies or Th1/Th17-type TRM cells in the respiratory mucosa and allow transmission of B. pertussis to naive or even immunized hosts. In contrast, intranasally delivered pertussis vaccines based on attenuated bacteria, antibiotic-inactivated bacteria, OMV, or soluble antigens with potent mucosal adjuvants, generate IgA and Th1/Th17-type TRM cells in the lung and nasal tissue, as well as serum IgG. These responses protect against infection and prevent transmission of B. pertussis. Created in BioRender. Mills, K. (2026) https://BioRender.com/ng9p113.