44 research outputs found
Trends in paediatric inpatient antibiotic therapy in a secondary care setting
There is growing attention for antimicrobial stewardship in paediatrics. Currently, little is known about secondary care antibiotic practice. We analysed trends in time with respect to inpatient antibiotic use in a secondary paediatric care setting. Total inpatient antibiotic consumption per year (2010–2015) and antibiotic prescriptions for urinary tract infection (UTI) and lower respiratory tract infection (LRTI) were analysed. Variables were total, antibiotic-specific, and intravenous days of therapy (DOT/100PD) and for UT
Development of a hypoallergenic recombinant parvalbumin for first-in-man subcutaneous immunotherapy of fish allergy.
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This article is open access.The FAST (food allergy-specific immunotherapy) project aims at developing safe and effective subcutaneous immunotherapy for fish allergy, using recombinant hypoallergenic carp parvalbumin, Cyp c 1.Preclinical characterization and good manufacturing practice (GMP) production of mutant Cyp (mCyp) c 1.Escherichia coli-produced mCyp c 1 was purified using standard chromatographic techniques. Physicochemical properties were investigated by gel electrophoresis, size exclusion chromatography, circular dichroism spectroscopy, reverse-phase high-performance liquid chromatography and mass spectrometry. Allergenicity was assessed by ImmunoCAP inhibition and basophil histamine release assay, immunogenicity by immunization of laboratory animals and stimulation of patients' peripheral blood mononuclear cells (PBMCs). Reference molecules were purified wild-type Cyp c 1 (natural and/or recombinant). GMP-compliant alum-adsorbed mCyp c 1 was tested for acute toxicity in mice and rabbits and for repeated-dose toxicity in mice. Accelerated and real-time protocols were used to evaluate stability of mCyp c 1 as drug substance and drug product.Purified mCyp c 1 behaves as a folded and stable molecule. Using sera of 26 double-blind placebo-controlled food-challenge-proven fish-allergic patients, reduction in allergenic activity ranged from 10- to 5,000-fold (1,000-fold on average), but with retained immunogenicity (immunization in mice/rabbits) and potency to stimulate human PBMCs. Toxicity studies revealed no toxic effects and real-time stability studies on the Al(OH)3-adsorbed drug product demonstrated at least 20 months of stability.The GMP drug product developed for treatment of fish allergy has the characteristics targeted for in FAST: i.e. hypoallergenicity with retained immunogenicity. These results have warranted first-in-man immunotherapy studies to evaluate the safety of this innovative vaccine.info:eu-repo/grantAgreement/EC/FP7/20187
Lipopolysaccharide contamination in intradermal DNA vaccination : toxic impurity or adjuvant?
Purpose: Lipopolysaccharides (LPS) are known both as potential adjuvants for vaccines and as toxic impurity in pharmaceutical preparations. The aim of this study was to assess the role of LPS in intradermal
DNA vaccination administered by DNA tattooing.
Method: Micewere vaccinated with a model DNA vaccine (Luc-NP) with an increasing content of residual
LPS. The effect of LPS on systemic toxicity, antigen expression and cellular immunity was studied.
Results: The presence of LPS in the DNA vaccine neither induced systemic toxicity (as reflected by IL-6
concentration in serum), nor influenced antigen expression (measured by intravital imaging). Higher LPS
contents however, appeared to be associated with an elevated cytotoxic T-lymphocyte (CTL) response but
without reaching statistical significance. Interestingly, the DNA tattoo procedure by itself was shown
to induce a serum cytokine response that was at least as potent as that induced by parenteral LPS
administration.
Conclusion: LPS does not show toxicity in mice vaccinated by DNA tattooing at dose levels well above
those encountered in GMP-grade DNA preparations. Thus, residual LPS levels in the pharmaceutical range
are not expected to adversely affect clinical outcome of vaccination trials and may in fact have some
beneficial adjuvant effect. The observed pro-inflammatory effects of DNA tattoo may help explain the
high immunogenicity of this procedure