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.

Background Sialorrhea is common in children with neurological disorders and leads to social isolation, aspiration pneumonia and increased caregiver burden. Sialorrhea management includes anticholinergic medications and a variety of surgeries, but these are limited by side effects, recurrence and risks. Objective We present our method of salivary gland ablation, an interventional radiology treatment for sialorrhea, and report safety and efficacy data from pediatric patients who underwent salivary gland ablation. Materials and methods Salivary gland ablation uses image-guided sotradecol and ethanol dual-drug injection into the salivary glands. Submandibular and sublingual glands are injected percutaneously using ultrasound. Parotid glands are injected retrograde through Stensen ducts using fluoroscopy. We conducted a retrospective review of the medical records of patients who underwent salivary gland ablation at our institution between 2005 and 2019. Pre-and post-procedure Drooling Frequency and Drooling Severity (DFDS) scale scores were compared and caregiver satisfaction was assessed. We devised two cohorts, one to study patient safety and a subcohort to study clinical efficacy using DFDS scores. Results One hundred and seventy salivary gland ablation procedures were performed in the 99 patients comprising the safety cohort. Of the procedures, 88.8% resulted in no or minimal complications. Respiratory difficulty, temporary nerve palsy and infection represent the majority of the 11.2% of patients who experienced periprocedural complications. There were no complications resulting in permanent sequelae. Twenty-seven patients met our inclusion criteria for the efficacy subcohort with a mean follow-up time of 5.4 years. DFDS at follow-up decreased from a median score of nine to a seven post-procedure (P=0.000018). The proportion of caregivers who were satisfied with the procedure increased as more glands were ablated, which suggests a causal link between the number of glands ablated and the outcome. Conclusion Salivary gland ablation is a safe and effective procedure with the potential for permanent decrease in symptoms related to sialorrhea.

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