688 research outputs found

    Characterization of potential biomarkers of reactogenicity of licensed antiviral vaccines: randomized controlled clinical trials conducted by the BIOVACSAFE consortium

    Get PDF
    Funding text The authors are grateful for the vital contributions of the participating study volunteers, clinicians, nurses, and laboratory technicians at the Surrey study site. The work by Roberto Leone, laboratory technician at Humanitas Clinical and Research Center, is gratefully acknowledged. Finally, they thank Ellen Oe (GSK) for scientific writing assistance. The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement n°115308, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007–2013) and EFPIA companies’ in-kind contribution. The contribution of the European Commission to the Advanced Immunization Technologies (ADITEC) project (grant agreement n° 280873) is also gratefully acknowledged. Publisher Copyright: © 2019, The Author(s).Biomarkers predictive of inflammatory events post-vaccination could accelerate vaccine development. Within the BIOVACSAFE framework, we conducted three identically designed, placebo-controlled inpatient/outpatient clinical studies (NCT01765413/NCT01771354/NCT01771367). Six antiviral vaccination strategies were evaluated to generate training data-sets of pre-/post-vaccination vital signs, blood changes and whole-blood gene transcripts, and to identify putative biomarkers of early inflammation/reactogenicity that could guide the design of subsequent focused confirmatory studies. Healthy adults (N = 123; 20–21/group) received one immunization at Day (D)0. Alum-adjuvanted hepatitis B vaccine elicited vital signs and inflammatory (CRP/innate cells) responses that were similar between primed/naive vaccinees, and low-level gene responses. MF59-adjuvanted trivalent influenza vaccine (ATIV) induced distinct physiological (temperature/heart rate/reactogenicity) response-patterns not seen with non-adjuvanted TIV or with the other vaccines. ATIV also elicited robust early (D1) activation of IFN-related genes (associated with serum IP-10 levels) and innate-cell-related genes, and changes in monocyte/neutrophil/lymphocyte counts, while TIV elicited similar but lower responses. Due to viral replication kinetics, innate gene activation by live yellow-fever or varicella-zoster virus (YFV/VZV) vaccines was more suspended, with early IFN-associated responses in naïve YFV-vaccine recipients but not in primed VZV-vaccine recipients. Inflammatory responses (physiological/serum markers, innate-signaling transcripts) are therefore a function of the vaccine type/composition and presence/absence of immune memory. The data reported here have guided the design of confirmatory Phase IV trials using ATIV to provide tools to identify inflammatory or reactogenicity biomarkers.Peer reviewe

    Magnetic resonance imaging studies of spontaneous capillary water imbibition in aerated gypsum

    Full text link
    International audienceIn this paper we investigate both capillary water imbibition and the sorptivity of aerated gypsum plaster, and how these sorption characteristics are related to the pore structure of the material. These characteristics are examined by monitoring mass change using the conventional gravimetric method and by obtaining water content profiles using nondestructive magnetic resonance imaging (MRI) techniques during capillary imbibition of water. Here, three different gypsum samples are investigated: one non-aerated reference gypsum sample and two aerated gypsum samples produced with different volumetric air fractions. The capillary water absorption into the reference sample follows t 1/2 kinetics (Fickian diffusion), where t is the time of ingress. However, in the aerated gypsum samples there are deviations from t 1/2 kinetics. The MRI results show unambiguously that two wetting fronts advance through the aerated structure ; an observation that cannot be made from the gravimetric data alone. The water content profiles of the aerated gypsum samples are therefore analysed by treating them as the sum of two separate absorption processes using Sharp Front (SF) analysis. The capillary water absorption properties of this material are well described as a parallel combination of fast absorption into fine matrix pores and slow absorption into a modified structure of matrix pores inter-connected to air voids introduced into the slurry by aeration. PACS 47.56.+r. flows through porous media PACS 47.55.nb. capillary and thermocapillary flow

    A phase II, open-label, multicentre study to evaluate the immunogenicity and safety of an adjuvanted prepandemic (H5N1) influenza vaccine in healthy Japanese adults

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Promising clinical data and significant antigen-sparing have been demonstrated for a pandemic H5N1 influenza split-virion vaccine adjuvanted with AS03<sub>A</sub>, an α-tocopherol-containing oil-in-water emulsion-based Adjuvant System. Although studies using this formulation have been reported, there have been no data for Japanese populations. This study therefore aimed to assess the immunogenicity and tolerability of a prepandemic (H5N1) influenza vaccine adjuvanted with AS03<sub>A </sub>in Japanese adults.</p> <p>Methods</p> <p>This open-label, single-group study was conducted at two centres in Japan in healthy Japanese males and females aged 20-64 years (n = 100). Subjects received two doses of vaccine, containing 3.75 μg haemagglutinin of the A/Indonesia/5/2005-like IBCDC-RG2 Clade 2.1 (H5N1) strain adjuvanted with AS03<sub>A</sub>, 21 days apart. The primary endpoint evaluated the humoral immune response in terms of H5N1 haemagglutination inhibition (HI) antibody titres against the vaccine strain (Clade 2.1) 21 days after the second dose. Ninety five percent confidence intervals for geometric mean titres, seroprotection, seroconversion and seropositivity rates were calculated. Secondary and exploratory endpoints included the assessment of the humoral response in terms of neutralising antibody titres, the response against additional H5N1 strains (Clade 1 and Clade 2.2), as well as the evaluation of safety and reactogenicity.</p> <p>Results</p> <p>Robust immune responses were elicited after two doses of the prepandemic influenza vaccine adjuvanted with AS03<sub>A</sub>. Overall, vaccine HI seroconversion rates and seroprotection rates were 91% 21 days after the second vaccination. This fulfilled all regulatory acceptance criteria for the vaccine-homologous HI antibody level. A substantial cross-reactive humoral immune response was also observed against the virus strains A/turkey/Turkey/1/2005 (Clade 2.2) and A/Vietnam/1194/2004 (Clade 1) after the second vaccine administration. A marked post-vaccination response in terms of neutralising antibody titres was demonstrated and persistence of the immune response was observed 6 months after the first dose. The vaccine was generally well tolerated and there were no serious adverse events reported.</p> <p>Conclusions</p> <p>The H5N1 candidate vaccine adjuvanted with AS03<sub>A </sub>elicited a strong and persistent immune response against the vaccine strain A/Indonesia/5/2005 in Japanese adults. Vaccination with this formulation demonstrated a clinically acceptable reactogenicity profile and did not raise any safety concerns in this population.</p> <p>Trial registration</p> <p>Clinicaltrials.gov NCT00742885</p

    Porosity estimation of (Moso bamboo) by computed tomography and backscattered electron imaging

    Get PDF
    This study aims to investigate and quantify the porosity in the cross section of Phyllostachys edulis (Moso bamboo) culm wall. The porosity results are expected to be utilised in numerical study of heat and moisture transfer. Computed tomography (CT) and backscattered electron (BSE) imaging methods are utilised in this study because these two methods allow measurements of the anisotropic features of bamboo specimens. The results of these two methods can be represented as the function of the real dimension rather than the pore size distribution of the specimen. The specimens are obtained from eight different locations along the Moso bamboo culms. Both internodes and nodes specimens are measured in this study. The average porosity, standard deviation (SD) and coefficient of variation (COV) are calculated for BSE and CT results. Pearson product-moment correlation coefficient (PPMCC) is also calculated in this study to analyse the correlation between the BSE results and CT results. Typical porosity results from 400 sampling points and 10 portions average porosity are analysed in this study. The CT scanning results show similar trend with BSE results. The correlation relationship between BSE and CT results approaches moderate correlation level to strong correlation level. The average porosity of internode specimens is from 43.9 to 58.8 % by BSE measurement and from 44.9 to 63.4 % by CT measurement. The average porosity of node specimens is from 37.4 to 56.6 % by BSE measurement and from 32.1 to 62.2 % by CT measurement

    Porosity estimation of Phyllostachys edulis (Moso bamboo) by computed tomography and backscattered electron imaging

    Get PDF
    This study aims to investigate and quantify the porosity in the cross section of Phyllostachys edulis (Moso bamboo) culm wall. The porosity results are expected to be utilised in numerical study of heat and moisture transfer. Computed tomography (CT) and backscattered electron (BSE) imaging methods are utilised in this study because these two methods allow measurements of the anisotropic features of bamboo specimens. The results of these two methods can be represented as the function of the real dimension rather than the pore size distribution of the specimen. The specimens are obtained from eight different locations along the Moso bamboo culms. Both internodes and nodes specimens are measured in this study. The average porosity, standard deviation (SD) and coefficient of variation (COV) are calculated for BSE and CT results. Pearson product-moment correlation coefficient (PPMCC) is also calculated in this study to analyse the correlation between the BSE results and CT results. Typical porosity results from 400 sampling points and 10 portions average porosity are analysed in this study. The CT scanning results show similar trend with BSE results. The correlation relationship between BSE and CT results approaches moderate correlation level to strong correlation level. The average porosity of internode specimens is from 43.9 to 58.8 % by BSE measurement and from 44.9 to 63.4 % by CT measurement. The average porosity of node specimens is from 37.4 to 56.6 % by BSE measurement and from 32.1 to 62.2 % by CT measurement

    Clinical Manifestations and Case Management of Ebola Haemorrhagic Fever caused by a newly identified virus strain, Bundibugyo, Uganda, 2007-2008

    Get PDF
    A confirmed Ebola haemorrhagic fever (EHF) outbreak in Bundibugyo, Uganda, November 2007-February 2008, was caused by a putative new species (Bundibugyo ebolavirus). It included 93 putative cases, 56 laboratory-confirmed cases, and 37 deaths (CFR = 25%). Study objectives are to describe clinical manifestations and case management for 26 hospitalised laboratory-confirmed EHF patients. Clinical findings are congruous with previously reported EHF infections. The most frequently experienced symptoms were non-bloody diarrhoea (81%), severe headache (81%), and asthenia (77%). Seven patients reported or were observed with haemorrhagic symptoms, six of whom died. Ebola care remains difficult due to the resource-poor setting of outbreaks and the infection-control procedures required. However, quality data collection is essential to evaluate case definitions and therapeutic interventions, and needs improvement in future epidemics. Organizations usually involved in EHF case management have a particular responsibility in this respect
    • …
    corecore