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.
Immunoglobulin G4-related disease (IgG4-RD) is a rare fibroinflammatory immune-mediated condition which can affect multiple organ systems and form mass-like lesions. Initial presentation can mimic other diseases such as pancreatic malignancy when there is pancreatic involvement or tuberculosis (TB) when there are pulmonary lesions or hypertrophic pachymeningitis (HP). Here, we report a novel case of IgG4-RD presenting as bilateral subdural haematomas with additional findings. Our patient is a male who presented with headaches and blurred vision. Physical examination showed disconjugate gaze with a fixed pupil. Trauma survey radiologic imaging revealed a pancreatic mass concerning for malignancy. Subsequent workup found hypophysitis with optic chiasm compression and hypopituitarism, mediastinal lymphadenopathy and HP. Laboratory values showed an elevated serum IgG4 level and latent TB. Our case adds to the existing IgG4-RD literature by highlighting a unique presentation. It is important to maintain it on the differential diagnosis especially in multisystemic presentations with competing diagnoses.
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