59 research outputs found

    Phytotropins

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    Quartz crystal microbalance sensors to elucidate interaction mechanisms between antigens and aluminum-based vaccine adjuvants

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    Vaccines are produced from antigenic subunits, such as proteins, which are poorly immunogenic, i.e. they fail to trigger a sufficient immune response and a memory effect, especially in children. The immunostimulation capacity of most vaccines is enhanced thanks to vaccine adjuvants, among which aluminum hydroxide (AH) is the most widely used. Antigen adsorption on AH adjuvant particles has been identified as an important step to produce effective vaccines. Controlling antigen-AH interactions is thus a key challenge in vaccine formulation. The aim of this work was to develop a new platform, based on quartz crystal microbalance (QCM), to monitor directly and in real time the adsorption of proteins, taken as model antigens, on adjuvant particles. The addressed challenges were (i) to assemble AH particles at the surface of QCM sensors into thin, continuous and stable layers, and (ii) to use these AH-modified sensors for the measurement of protein adsorption in different pH and ionic strength conditions, with a view to unravel adsorption mechanisms. The modified sensors were successfully elaborated with two different commercial AH adjuvants. The immobilized AH particle layers were thin (20-80 nm thick), stable under different pH and saline conditions, and reached a high surface coverage on the QCM sensors. The adsorption results revealed that bovine serum albumin (BSA) adsorption was not exclusively driven by electrostatic interactions at physiological pH. Moreover, the role of PO4-OH ligand exchanges was highlighted in the adsorption of ovalbumin, as well as in BSA adsorption, despite the fact that the latter has a low phosphate content. The two different AH adjuvants behaved differently towards protein adsorption, even though their physicochemical properties were similar. The immobilization of adjuvant particles on QCM sensors offers a new platform for the study of antigen adsorption, to the benefit of vaccine formulation, and also enriches the range of applications for which QCM can be exploited, especially in colloid science.(AGRO - Sciences agronomiques et ingénierie biologique) -- UCL, 201

    Use of a quartz crystal microbalance platform to study protein adsorption on aluminum hydroxide vaccine adjuvants: Focus on phosphate-hydroxide ligand exchanges

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    Aluminum hydroxide (AH) salts are widely used as vaccine adjuvants and controlling antigen-AH interactions is a key challenge in vaccine formulation. In a previous work, we have developed a quartz crystal microbalance (QCM) platform, based on stable AH-coated sensors, to explore the mechanisms of model antigen adsorption. The QCM study of bovine serum albumin (BSA) adsorption at different pH and ionic strength (I) values showed that protein adsorption on AH adjuvant at physiological pH cannot be explained mainly by electrostatic interactions, in contrast with previous reports. Here, we exploit further the developed QCM platform to investigate the role of phosphate-hydroxyl ligand exchanges in the adsorption mechanism of BSA, human serum albumin (HSA) and ovalbumin (OVA) on two commercial AH adjuvants. BSA adsorption decreased on immobilized AH particles previously treated with KH2PO4, highlighting the role of exchangeable sites on AH particles in the adsorption process. BSA and OVA were dephosphorylated by treatment with an acid phosphatase to decrease their phosphate content by about 80% and 25%, respectively. Compared to native BSA, adsorption of dephosphorylated BSA decreased significantly on one AH adjuvant at pH 7. Adsorption of dephosphorylated OVA was comparable to the one of native OVA. Further QCM assays showed that phospho-amino acids (PO4-serine and PO4-threonine) displaced previously adsorbed BSA and OVA from AH particles in conditions that were depending on the protein and the AH. Taken together, these observations suggest that phosphate-hydroxyl ligand exchange is an important adsorption mechanism of proteins on AH. These results moreover confirm that the developed AH-coated QCM sensors offer a new platform for the study of antigen adsorption, to the benefit of vaccine formulation

    NaCl strongly modifies the physicochemical properties of aluminum hydroxide vaccine adjuvants

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    The immunostimulation capacity of most vaccines is enhanced through antigen adsorption on aluminum hydroxide (AH) adjuvants. Varying the adsorption conditions, i.e. pH and ionic strength (I), changes the antigen adsorbed amount and therefore the ability of the vaccine to stimulate the immune system. Vaccine formulations are thus resulting from an empirical screening of the adsorption conditions. This work aims at studying the physicochemical effects of adjusting the ionic strength of commercial AH adjuvant particles suspensions with sodium chloride (NaCl). X-ray photoelectron spectroscopy data show that AH particles surface chemical composition is neither altered by I adjustment with NaCl nor by deposition on gold surfaces. The latter result provides the opportunity to use AH-coated gold surfaces as a platform for advanced surface analysis of adjuvant particles, e.g. by atomic force microscopy (AFM). The morphology of adjuvant particles recovered from native and NaCl-treated AH suspensions, as studied by scanning electron microscopy and AFM, reveals that AH particles aggregation state is significantly altered by NaCl addition. This is further confirmed by nitrogen adsorption experiments: I adjustment to 150 mM with NaCl strongly promotes AH particles aggregation leading to a strong decrease of the developed specific surface area. This work thus evidences the effect of NaCl on AH adjuvant structure, which may lead to alteration of formulated vaccines and to misinterpretation of data related to antigen adsorption on adjuvant particles

    Laparoscopic Cholecystectomy - a Multicenter Belgian Experience

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    In a Belgian multicenter study 507 patients were submitted to an attempt of laparoscopic cholecystectomy. 78% of the patients had uncomplicated gallstones whereas 22% had complicated ones. 40% of the patients were operated on by a surgeon with coelioscopic experience of less than 25 cases. A laparotomy was required in 5.5% of the patients. Hospital mortality was 0.4% and overall morbidity 7.3%: general complications occurred in 2% of the patients and local complications in 5.3% including minor complications in 3.1% and major complications in 2.2%. Reintervention was necessary in 1.4%. Residual common bile duct stones were detected in 1.2%. The mean postoperative hospital stay was 4.28 days. The benefit of laparoscopic cholecystectomy is essentially functional. Adequate teaching of coelioscopy in surgical training is mandatory to avoid unnecessary morbidity
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