Local and Systemic Immunity against Respiratory Syncytial Virus Induced by a Novel Intranasal Vaccine. A Randomized, Double-Blind, Placebo-controlled Clinical Trial.

Rationale: Needle-free intranasal vaccines offer major potential advantages, especially against pathogens entering via mucosal surfaces. As yet, there is no effective vaccine against respiratory syncytial virus (RSV), a ubiquitous pathogen of global importance that preferentially infects respiratory epithelial cells; new strategies are urgently required.Objectives: Here, we report the safety and immunogenicity of a novel mucosal RSV F protein vaccine linked to an immunostimulatory bacterium-like particle (BLP).Methods: In this phase I, randomized, double-blind, placebo-controlled trial, 48 healthy volunteers, aged 18-49 years, were randomly assigned to receive placebo or SynGEM (low or high dose) intranasally by prime-boost administration. The primary outcome was safety and tolerability, with secondary objectives assessing virus-specific immunogenicity.Measurements and Main Results: There were no significant differences in adverse events between placebo and vaccinated groups. SynGEM induced systemic plasmablast responses and significant, durable increases in RSV-specific serum antibody in healthy, seropositive adults. Volunteers given low-dose SynGEM (140 µg F, 2 mg BLP) required a boost at Day 28 to achieve plateau responses with a maximum fold change of 2.4, whereas high-dose recipients (350 µg F, 5 mg BLP) achieved plateau responses with a fold change of 1.5 after first vaccination that remained elevated up to 180 days after vaccination, irrespective of further boosting. Palivizumab-like antibodies were consistently induced, but F protein site ∅-specific antibodies were not detected, and virus-specific nasal IgA responses were heterogeneous, with the strongest responses in individuals with lower pre-existing antibody levels.Conclusions: SynGEM is thus the first nonreplicating intranasal RSV subunit vaccine to induce persistent antibody responses in human volunteers.Clinical trials registered with www.clinicaltrials.gov (NCT02958540).

The association between occupational secondhand smoke exposure and life satisfaction among adults in the European Union.

BACKGROUND: Despite existing legislation, a large proportion of the European Union (EU) population is exposed to occupational secondhand smoke (SHS). The aim of this study was to explore associations between occupational exposure to SHS and self-reported life satisfaction. METHODS: We analysed data collected through the Eurobarometer survey (wave 82.4) from n = 11,788 individuals working in indoor spaces. The sample was representative of the population of the 28 EU member states. We fitted a multilevel logistic regression model adjusting for smoking, age, gender, occupation, area of residence, education, difficulty paying bills, marital status and social class. RESULTS: 27.5% of those working indoors reported at least some occupational exposure to SHS. People exposed to occupational SHS were less likely to report that they were satisfied with the life they lead (adjusted Odds Ratio = 0.72, 95% Confidence Interval: 0.60-0.87). The effect of occupational exposure on life satisfaction did not differ by smoking status, with all interaction terms between smoking status and occupational exposure to SHS not statistically significant. CONCLUSION: Exposure to SHS at the workplace does not only have negative consequences on physical health, but it can also impact life satisfaction of smokers and non-smokers. Our findings highlight the need for stricter enforcement of smokefree environments at the workplace in the EU.

Effects of continuous positive airway pressure (CPAP) treatment for obstructive sleep apnea in arterial stiffness: a meta-analysis.

Obstructive sleep apnea (OSA) is associated with increased arterial stiffness, a cumulative indicator of arterial health. Continuous positive airway pressure (CPAP) is the gold standard treatment for OSA. We conducted a meta-analysis of the available literature investigating the effect of CPAP on arterial stiffness in patients with OSA. Fifteen articles (n = 615 patients) assessing indices of arterial stiffness were identified. Five different meta-analyses were performed assessing: a) all indices of arterial stiffness, b) augmentation index (AIx), c) all pulse wave velocities (PWV), d) brachial-ankle PWV and e) carotid-femoral PWV. Pooled standardized mean differences (SMDs) and weighted mean differences (WMDs) were appropriately calculated through fixed or random effects models after assessing between-study heterogeneity. A significant improvement of all indices of arterial stiffness was observed after CPAP treatment (SMD = -0.74; 95%CI: -1.08 to -0.41). AIx and PWVs were also significantly improved (WMD = -4.86; 95%CI: -7.31 to -2.41 and WMD = -0.87; 95%CI: -0.98 to -0.77, respectively), as well as brachial-ankle PWV and carotid-femoral PWV (WMD = -0.86; 95%CI: -0.97 to -0.75 and WMD = -1.21; 95%CI:-1.92 to -0.50, respectively). Neither the proportion of compliant patients nor the duration of CPAP use altered the effect of arterial stiffness reduction after CPAP treatment. In conclusion, our meta-analyses showed significant improvements in all indices of arterial stiffness after CPAP treatment in patients with OSA. As clinical use of arterial stiffness is growing in popularity, the efficacy of this useful tool in assessing cardiovascular risk reduction among patients with OSA treated with CPAP needs to be further explored.

Serum adiponectin as a predictor of childhood non-Hodgkin's lymphoma: a nationwide case-control study.

PURPOSE: To our knowledge, this is the first study exploring the association of childhood non-Hodgkin's lymphoma (NHL) with serum adiponectin and leptin levels in a nationwide case-control series. In addition, expression of adiponectin receptors in NHL specimens was assessed, and the association between adipokines and childhood NHL survival and prognosis was examined. PATIENTS AND METHODS: We studied 121 incident childhood (0 to 14 years) NHL cases registered in the Nationwide Registry for Childhood Hematological Malignancies (1996 to 2006) and an equal number of matched controls, for whom sociodemographic, lifestyle, prenatal characteristics, and fasting blood serums were collected. Serum adiponectin and leptin levels were determined. Immunohistochemisty for adiponectin receptors expression was performed on commercially available adult NHL specimens (n = 30) and in a subset of childhood NHL cases (n = 6) that were available. Summary statistics, multiple conditional logistic regression analyses, and survival analysis were performed. RESULTS: Higher serum adiponectin, but not leptin, levels were independently associated with childhood NHL (odds ratio, 1.82; 95% CI, 1.30 to 2.56), after adjusting for obesity and established risk factors. Higher adiponectin levels at diagnosis were positively associated with relapse and poor survival, but hormone levels did not differ among NHL subtypes. Adiponectin receptors 1 and 2 were present in 90% and 57% of adult samples and in 83% and 100% of childhood NHL samples, respectively. CONCLUSION: Elevated serum adiponectin, but not leptin, levels are independently associated with childhood NHL and poor prognosis. Adiponectin receptors are expressed in NHL, suggesting that adiponectin may represent not only a potential clinically significant diagnostic and prognostic marker but also a molecule that may be implicated in NHL pathogenesis.