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Le Pont-de-Claix, France

Felsovalyi F.,Columbia University | Felsovalyi F.,United Medical Systems | Patel T.,Columbia University | Mangiagalli P.,BD Medical Pharmaceutical Systems | And 2 more authors.
Protein Science | Year: 2012

Gaining more insight into the mechanisms governing the behavior of proteins at solid/liquid interfaces is particularly relevant in the interaction of high-value biologics with storage and delivery device surfaces, where adsorption-induced conformational changes may dramatically affect biocompatibility. The impact of structural stability on interfacial behavior has been previously investigated by engineering nonwild-type stability mutants. Potential shortcomings of such approaches include only modest changes in thermostability, and the introduction of changes in the topology of the proteins when disulfide bonds are incorporated. Here we employ two members of the aldo-keto reductase superfamily (alcohol dehydrogenase, AdhD and human aldose reductase, hAR) to gain a new perspective on the role of naturally occurring thermostability on adsorbed protein arrangement and its subsequent impact on desorption. Unexpectedly, we find that during initial adsorption events, both proteins have similar affinity to the substrate and undergo nearly identical levels of structural perturbation. Interesting differences between AdhD and hAR occur during desorption and both proteins exhibit some level of activity loss and irreversible conformational change upon desorption. Although such surface-induced denaturation is expected for the less stable hAR, it is remarkable that the extremely thermostable AdhD is similarly affected by adsorption-induced events. These results question the role of thermal stability as a predictor of protein adsorption/desorption behavior. © 2012 The Protein Society. Source


Le Luduec J.-B.,University of Lyon | Le Luduec J.-B.,French Institute of Health and Medical Research | Le Luduec J.-B.,Ecole Normale Superieure de Lyon | Le Luduec J.-B.,French National Center for Scientific Research | And 16 more authors.
Vaccine | Year: 2016

Intradermal (ID) vaccination constitutes a promising approach to induce anti-infectious immunity. This route of immunization has mostly been studied with influenza split-virion vaccines. However, the efficacy of ID vaccination for sub-unit vaccines in relation to underlying skin innate immunity remains to be explored for wider application in humans. Relevant animal models that more closely mimic human skin immunity than the widely used mouse models are therefore necessary. Here, we show in domestic swine, which shares striking anatomic and functional properties with human skin, that a single ID delivery of pseudorabies virus (PRV) glycoproteins without added adjuvant is sufficient to trigger adaptive cellular and humoral immune responses, and to confer protection from a lethal respiratory infection with PRV. Analysis of early events at the skin injection site revealed up-regulation of pro-inflammatory cytokine and chemokine genes, recruitment of neutrophils and monocytes and accumulation of inflammatory DC. We further show that the sustained induction of pro-inflammatory cytokine genes results from the combined effects of skin puncture, liquid injection in the dermis and viral antigens. These data highlight that immune protection against respiratory infection can be induced by ID vaccination with a subunit vaccine and reveal that adjuvant requirements are circumvented by the mechanical and antigenic stress caused by ID injection, which triggers innate immunity and mobilization of inflammatory DC at the immunization site. ID vaccination with sub-unit vaccines may thus represent a safe and efficient solution for protection against respiratory infections in swine and possibly also in humans, given the similarity of skin structure and function in both species. © 2016 Elsevier Ltd. Source


Maden A.,BD Medical Pharmaceutical Systems | O'Sullivan K.,BD Medical
ONdrugDelivery | Year: 2015

In this piece, Alice Maden, PharmD, Global and Regional Regulatory Affairs Manager, and Kathleen O’Sullivan, MS, RAC, Worldwide Director, Regulatory Affairs, both of BD Medical, take the practical example of a drug product filled in a BD Hypak™ glass prefillable syringe to describe how the worldwide regulatory environment of combination products has rapidly evolved. BD’s Regulatory Affairs team has adapted their support offerings and customised solutions to assist customers from the pharmaceutical and biotechnology industry to sustain this major change. © 2015 Frederick Furness Publishing Ltd. Source


Laurent P.E.,BD Medical Pharmaceutical Systems | Bourhy H.,Institute Pasteur Paris | Fantino M.,University of Burgundy | Alchas P.,United Medical Systems | Mikszta J.A.,Research Triangle Park
Vaccine | Year: 2010

In the present pilot study, intradermal ID delivery systems with a BD microneedle from 1 to 3. mm in length, and epidermal delivery (BD skin abrader) through abraded skin surface relative to standard intramuscular injection were evaluated. Circulating neutralizing antibodies were measured against the rabies virus after the Vero cells rabies vaccine was administered at D0, D7, D21 and D49. This clinical evaluation in 66 healthy volunteers shows that ID delivery using BD microneedle technology of 1/4 the IM antigen dose is safe, efficient and reliable, resulting in a protective seroconversion rate. In contrast, the epidermal delivery route did not produce an immune response against the rabies vaccine. © 2010 Elsevier Ltd. Source


Felsovalyi F.,Columbia University | Felsovalyi F.,United Medical Systems | Mangiagalli P.,BD Medical Pharmaceutical Systems | Bureau C.,BD Medical Pharmaceutical Systems | And 2 more authors.
Langmuir | Year: 2011

A central paradigm that underpins our understanding of the interaction of proteins with solid surfaces is that protein adsorption leads to changes in secondary structure. The bound proteins tend to denature, and these non-native, adsorbed structures are likely stabilized through the loss of α-helices with the concomitant formation of intermolecular β-sheets. The goal of this work is to critically assess the impact this behavior has on protein desorption, where irreversible conformational changes might lead to protein aggregation or result in other forms of instability. The adsorption, desorption, and structural transitions of lysozyme are examined on fumed silica nanoparticles as a function of the amount of protein adsorbed. Surprisingly, the data indicate not only that adsorption is reversible but also that protein desorption is predictable in a coverage-dependent manner. Additionally, there is evidence of a two-state model which involves exchange between a native-like dissolved state and a highly perturbed adsorbed state. Since the in situ circular dichroism (CD) derived secondary structures of the adsorbed proteins are essentially unaffected by changes in surface coverage, these results are not consistent with previous claims that surface-induced denaturation is coverage dependent. Inspired by results from homopolymer adsorption experiments, we speculate that more local descriptors, such as the number of amino acids per chain that are physically adsorbed on the surface, likely control the desorption process. © 2011 American Chemical Society. Source

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