Safety and immunogenicity of live, attenuated intranasal Bordetella pertussis vaccine (BPZE1) in healthy adults.

BACKGROUND: BPZE1 is a live, attenuated pertussis vaccine derived from B. pertussis strain Tohama I modified by genetic removal or inactivation of 3 B. pertussis toxins: pertussis toxin, dermonecrotic toxin, and tracheal cytotoxin. This Phase 2a study evaluated the safety and immunogenicity of liquid or lyophilized BPZE1 vaccine administered intranasally by needleless tuberculin syringe or mucosal atomization device (VaxINatorTM) at two dose levels. METHODS: Fifty healthy male and non-pregnant female participants 18-49 years of age were enrolled. Participants were randomized 3:3:3:1 to a single lyophilized dose of 107 colony forming units (CFU) BPZE1, 109 CFU BPZE1, placebo via VaxINator device, or a single liquid dose of 109 CFU BPZE1 via tuberculin syringe. Reactogenicity was assessed for 14 days. Blood was obtained pre-vaccination; on Day 8 (safety); and on Days 15, 29, and 181 (immunogenicity). Nasal wick and swab samples were obtained at baseline and on Days 29 and 181 for assessment of mucosal antibody responses and clearance of BPZE1. RESULTS: Across all groups, 35/50 (70 %) experienced at least one local adverse event (AE) and 31/50 (62 %) experienced at least one systemic AE, with similar AE frequencies observed between the highest 109 CFU BPZE1 and placebo groups. There were no severe or serious AEs during the study. At Day 29, seroconversion (≥2-fold rise from baseline in serum IgG or IgA) to at least 2 pertussis antigens was observed in 73 % in the 109 CFU BPZE1 VaxINator group, 60 % in the 109 CFU BPZE1 group delivered via tuberculin syringe, 27 % of participants in the 107 CFU BPZE1 VaxINator group, and 20 % in the placebo VaxINator group. No participants were colonized with BPZE1 at Day 29 post vaccination. DISCUSSION: Lyophilized BPZE1 vaccine was well tolerated and immunogenic at the highest dose (109 CFU) delivered intranasally by VaxINator device and was not associated with any SAEs or prolonged shedding of BPZE1. Further evaluation of BPZE1 is warranted.

Safety of Live Attenuated Influenza Vaccine in Children With Asthma.

BACKGROUND AND OBJECTIVES: Asthma is considered a precaution for use of quadrivalent live attenuated influenza vaccine (LAIV4) in persons aged ≥5 years because of concerns for wheezing events. We evaluated the safety of LAIV4 in children with asthma, comparing the proportion of children with asthma exacerbations after LAIV4 or quadrivalent inactivated influenza vaccine (IIV4). METHODS: We enrolled 151 children with asthma, aged 5 to 17 years, during 2 influenza seasons. Participants were randomly assigned 1:1 to receive IIV4 or LAIV4 and monitored for asthma symptoms, exacerbations, changes in peak expiratory flow rate (PEFR), and changes in the asthma control test for 42 days after vaccination. RESULTS: We included 142 participants in the per-protocol analysis. Within 42 days postvaccination, 18 of 142 (13%) experienced an asthma exacerbation: 8 of 74 (11%) in the LAIV4 group versus 10 of 68 (15%) in the IIV4 group (LAIV4-IIV4 = -0.0390 [90% confidence interval -0.1453 to 0.0674]), meeting the bounds for noninferiority. When adjusted for asthma severity, LAIV4 remained noninferior to IIV4. There were no significant differences in the frequency of asthma symptoms, change in PEFR, or childhood asthma control test/asthma control test scores in the 14 days postvaccination between LAIV4 and IIV4 recipients. Vaccine reactogenicity was similar between groups, although sore throat (P = .051) and myalgia (P <.001) were more common in the IIV4 group. CONCLUSIONS: LAIV4 was not associated with increased frequency of asthma exacerbations, an increase in asthma-related symptoms, or a decrease in PEFR compared with IIV4 among children aged 5 to 17 years with asthma.

Variability in the Management of Adults With Pulmonary Nontuberculous Mycobacterial Disease.

BACKGROUND: The increasing global prevalence of pulmonary nontuberculous mycobacteria (NTM) disease has called attention to challenges in NTM diagnosis and management. This study was conducted to understand management and outcomes of patients with pulmonary NTM disease at diverse centers across the United States. METHODS: We conducted a 10-year (2005-2015) retrospective study at 7 Vaccine and Treatment Evaluation Units to evaluate pulmonary NTM treatment outcomes in human immunodeficiency virus-negative adults. Demographic and clinical information was abstracted through medical record review. Microbiologic and clinical cure were evaluated using previously defined criteria. RESULTS: Of 297 patients diagnosed with pulmonary NTM, the most frequent NTM species were Mycobacterium avium-intracellulare complex (83.2%), M. kansasii (7.7%), and M. abscessus (3.4%). Two hundred forty-five (82.5%) patients received treatment, while 45 (15.2%) were followed without treatment. Eighty-six patients had available drug susceptibility results; of these, >40% exhibited resistance to rifampin, ethambutol, or amikacin. Of the 138 patients with adequate outcome data, 78 (56.5%) experienced clinical and/or microbiologic cure. Adherence to the American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) treatment guidelines was significantly more common in patients who were cured (odds ratio, 4.5, 95% confidence interval, 2.0-10.4; P < .001). Overall mortality was 15.7%. CONCLUSIONS: Despite ATS/IDSA Guidelines, management of pulmonary NTM disease was heterogeneous and cure rates were relatively low. Further work is required to understand which patients are suitable for monitoring without treatment and the impact of antimicrobial therapy on pulmonary NTM morbidity and mortality.