Abstract
Current acellular pertussis vaccines fall short of optimal protection against the human respiratory pathogen Bordetella pertussis resulting in increased incidence of a previously controlled vaccine- preventable disease. Natural infection is known to induce a protective mucosal immunity. Therefore, in this study, we aimed to use acellular pertussis vaccines to recapitulate these mucosal immune responses. We utilized a murine immunization and challenge model to characterize the efficacy of intranasal immunization (IN) with DTaP vaccine or DTaP vaccine supplemented with curdlan, a known Th1/Th17 promoting adjuvant. Protection from IN delivered DTaP was compared to protection mediated by intraperitoneal injection of DTaP and whole-cell pertussis vaccines. We tracked fluorescently labeled DTaP after immunization and detected that DTaP localized preferentially in the lungs while DTaP with curdlan was predominantly in the nasal turbinates. IN immunization with DTaP, with or without curdlan adjuvant, resulted in anti-B. pertussis and anti-pertussis toxin IgG titers at the same level as intraperitoneally administered DTaP. IN immunization was able to protect against B. pertussis challenge and we observed decreased pulmonary pro-inflammatory cytokines, neutrophil infiltrates in the lung, and bacterial burden in the upper and lower respiratory tract at day 3 post challenge. Furthermore, IN immunization with DTaP triggered mucosal immune responses such as production of B. pertussis-specific IgA, and increased IL-17A. Together, the induction of a mucosal immune response and humoral antibody-mediated protection associated with an IN administered DTaP and curdlan adjuvant warrant further exploration as a pertussis vaccine candidate formulation.
Highlights
Pertussis is a human upper respiratory disease, primarily caused by the Gram-negative pathogen Bordetella pertussis
We measured the size of the labeled particles and determined that size was similar to what has been previously reported, and labeled particles were on average were 1.52 ± 0.76 μm. These findings are comparable to Intranasal immunization induces production of anti-Pertussis toxin (PT) and antiFHA IgG in serum
The natural immune response to B. pertussis is initiated by the colonization of the respiratory tract, which leads to a cascade of inflammatory cytokines such as IL-6, IFN-γ, TNF-α, and IL-1β leading to increased inflammatory infiltrate consisting of: dendritic cells, macrophages, neutrophils, and lymphocytes.[42,46]
Summary
Pertussis is a human upper respiratory disease, primarily caused by the Gram-negative pathogen Bordetella pertussis. The disease is most severe in unvaccinated infants, where it manifests as fits of paroxysmal coughs followed by the classical whoop as air reenters the respiratory system, leading to the more commonly known name: whooping cough.[1] Additional complications include vomiting, increased mucus production, and apneic episodes. In severe cases, these symptoms can lead to elevated leukocytosis, pulmonary hypertension, hypoxia, and in some cases death.[1,2,3]. In the United States the number of pertussis cases has been increasing since the 1990s, despite high vaccine coverage.[7]
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