BackgroundWe have developed a recombinant B cell epitope-based vaccine (BM32) for allergen-specific immunotherapy (AIT) of grass pollen allergy. The vaccine contains recombinant fusion proteins consisting of allergen-derived peptides and the hepatitis B surface protein domain preS as immunological carrier.MethodsWe conducted a randomized, double-blind, placebo-controlled AIT study to determine safety, clinical efficacy and immunological mechanism of three subcutaneous injections of three BM32 doses adsorbed to aluminum hydroxide versus aluminum hydroxide (placebo) applied monthly to grass pollen allergic patients (n = 70). Primary efficacy endpoint was the difference in total nasal symptom score (TNSS) through grass pollen chamber exposure before treatment and 4 weeks after the last injection. Secondary clinical endpoints were total ocular symptom score (TOSS) and allergen-specific skin response evaluated by titrated skin prick testing (SPT) at the same time points. Treatment-related side effects were evaluated as safety endpoints. Changes in allergen-specific antibody, cellular and cytokine responses were measured in patients before and after treatment.ResultsSixty-eight patients completed the trial. TNSS significantly decreased with mean changes of − 1.41 (BM32/20 μg) (P = 0.03) and − 1.34 (BM32/40 μg) (P = 0.003) whereas mean changes in the BM32/10 μg and placebo group were not significant. TOSS and SPT reactions showed a dose-dependent decrease. No systemic immediate type side effects were observed. Only few grade 1 systemic late phase reactions occurred in BM32 treated patients. The number of local injection site reactions was similar in actively and placebo-treated patients. BM32 induced highly significant allergen-specific IgG responses (P < 0.0001) but no allergen-specific IgE. Allergen-induced basophil activation was reduced in BM32 treated patients and addition of therapy-induced IgG significantly suppressed T cell activation (P = 0.0063).ConclusionThe B cell epitope-based recombinant grass pollen allergy vaccine BM32 is well tolerated and few doses are sufficient to suppress immediate allergic reactions as well as allergen-specific T cell responses via a selective induction of allergen-specific IgG antibodies. (ClinicalTrials.gov number, NCT01445002.)

The relative and absolute numbers of very old patients increased over the study period, as did the severity of illness. Despite this, risk-adjusted hospital mortality improved over the study period. Females dominated in the very old patients and exhibited moreover a better outcome compared with males.

The epidemiology of chronic obstructive pulmonary disease (COPD) in critically ill patients is largely unknown. The aims of the study were: 1) to determine whether COPD, either as the cause of intensive care unit (ICU) admission or as a comorbid condition, is an independent risk factor for increased morbidity and mortality; and 2) to investigate time trends in proportion and outcome of acute respiratory failure in patients with COPD admitted to ICUs.Prospectively recorded data from 194 453 adults consecutively admitted to 87 Austrian ICUs over a period of 11 years (1998)(1999)(2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008) were retrospectively analysed.COPD was present in 8.6% of all patients. The risk-adjusted mortality of patients with COPD was higher than in patients without COPD. The presence of COPD was an independent risk factor for increased mortality and was associated with prolonged mechanical ventilation and prolonged weaning. During the course of the 11 years, the proportion of acute respiratory failure due to COPD increased by about two-thirds, and the use of noninvasive ventilation within the COPD cohort more than doubled. Simultaneously, the risk-adjusted mortality of patients with COPD improved.In critically ill patients, the presence of COPD is increasing and is an independent risk factor for mortality and morbidity.

Background Chronic hepatitis B virus (HBV) infections are a global health problem. There is a need for therapeutic strategies blocking continuous infection of liver cells. The grass pollen allergy vaccine BM32 containing the preS domain of the large HBV surface protein (LHBs) as immunogenic carrier induced IgG antibodies in human subjects inhibiting HBV infection in vitro . Aim of this study was the quantification, epitope mapping and investigation of HBV genotype cross-reactivity of preS-specific antibodies in subjects treated with different dosage regimens of BM32 Methods Hundred twenty eight grass pollen allergic patients received in a double-blind, placebo-controlled trial five monthly injections of placebo (aluminum hydroxide, n = 34) or different courses of BM32 (2 placebo + 3 BM32, n = 33; 1 placebo + 4 BM32, n = 30; 5 BM32, n = 31). Recombinant Escherichia coli -expressed preS was purified. Overlapping peptides spanning preS and the receptor-binding sites from consensus sequences of genotypes A–H were synthesized and purified. Isotype (IgM, IgG, IgA, IgE) and IgG subclass (IgG 1 -IgG 4 ) responses to preS and peptides were determined by ELISA at baseline, one and four months after the last injection. IgG 1 and IgG 4 subclass concentrations specific for preS and the receptor-binding site were measured by quantitative ELISA. Findings Five monthly injections induced the highest levels of preS-specific IgG consisting mainly of IgG 1 and IgG 4 , with a sum of median preS-specific IgG 1 and IgG 4 concentrations of >135 μg/ml reaching up to 1.8 mg/ml. More than 20% of preS-specific IgG was directed against the receptor-binding site. BM32-induced IgG cross-reacted with the receptor-binding domains from all eight HBV genotypes A-H. Interpretation BM32 induces high levels of IgG 1 and IgG 4 antibodies against the receptor binding sites of all eight HBV genotypes and hence might be suitable for therapeutic HBV vaccination. Funding This study was supported by the PhD program IAI (KPW01212FW), by Viravaxx AG and by the Danube-ARC funded by the Government of Lower Austria. Rudolf Valenta is a recipient of a Megagrant of the Government of the Russian Federation, grant No 14.W03.31.0024.

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