VLPs and particle strategies for cancer vaccines

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Microneedles: A New Frontier in Nanomedicine Delivery

This review aims to concisely chart the development of two individual research fields, namely nanomedicines, with specific emphasis on nanoparticles (NP) and microparticles (MP), and microneedle (MN) technologies, which have, in the recent past, been exploited in combinatorial approaches for the efficient delivery of a variety of medicinal agents across the skin. This is an emerging and exciting area of pharmaceutical sciences research within the remit of transdermal drug delivery and as such will undoubtedly continue to grow with the emergence of new formulation and fabrication methodologies for particles and MN. Firstly, the fundamental aspects of skin architecture and structure are outlined, with particular reference to their influence on NP and MP penetration. Following on from this, a variety of different particles are described, as are the diverse range of MN modalities currently under development. The review concludes by highlighting some of the novel delivery systems which have been described in the literature exploiting these two approaches and directs the reader towards emerging uses for nanomedicines in combination with MN

Using Dynamic Capabilities in an actionable tool as a vehicle to initiate design-driven innovation

In order to become more innovative, corporations are increasingly turning to design-driven innovation capabilities. These capabilities are dynamic: they influence the way companies run their business and how companies create, capture and deliver value. Building design capabilities has proven difficult, given the tacit nature of design practice and the conflicting reasoning style of abduction that allows for the creative leap. However, if these enterprises don’t improve, they are in danger of losing theirability to add value to the market. This may result in loss of market-share, which may lead to job destruction and the loss of valuable knowledge as communities of practice fall apart. This paper describes an iterative design process in which a tool was developed to determine which design-driven innovation capabilities a company is lacking. The tool started as a theoretical framework and was subsequently developed by prototyping with innovation managers from several large corporates. This paper contributes a new ‘dynamic capabilities view’ on design and innovation and a practical approach to implementing design in large firms. <br/

Designing interaction for next generation personal computing

Over two decades of research in the field of Interaction Design and Computer Supported Cooperative Work convinced us that the current design of workstations no longer fits users' needs. It is time to design new personal computers based on metaphors alternative to the desktop one. With this SIG, we are seeking to involve international HCI professionals into the challenges of designing products that are radically new and tackling the many different issues of modern knowledge workers. We would like to engage a wider cross-section of the community: our focus will be on issues of development and participation and the impact of different values in our work

Critical Role of TLR7 Signaling in the Priming of Cross-Protective Cytotoxic T Lymphocyte Responses by a Whole Inactivated Influenza Virus Vaccine

<p>Current influenza vaccines fail to induce protection against antigenically distinct virus strains. Accordingly, there is a need for the development of cross-protective vaccines. Previously, we and others have shown that vaccination with whole inactivated virus (WIV) induces cross-protective cellular immunity in mice. To probe the mechanistic basis for this finding, we investigated the role of TLR7, a receptor for single-stranded RNA, in induction of cross-protection. Vaccination of TLR7-/- mice with influenza WIV failed to protect against a lethal heterosubtypic challenge; in contrast, wild-type mice were fully protected. The lack of protection in TLR7-/- mice was associated with high viral load and a relative paucity of influenza-specific CD8+ cytotoxic T lymphocyte (CTL) responses. Dendritic cells (DCs) from TLR7-/- mice were unable to cross-present WIV-derived antigen to influenza-specific CTLs in vitro. Similarly, TLR7-/- DCs failed to mature and become activated in response to WIV, as determined by the assessment of surface marker expression and cytokine production. Plasmacytoid DCs (pDCs) derived from wild-type mice responded directly to WIV while purified conventional DCs (cDCs) did not respond to WIV in isolation, but were responsive in mixed pDC/cDC cultures. Depletion of pDCs prior to and during WIV immunization resulted in reduced numbers of influenza-specific CTLs and impaired protection from heterosubtypic challenge. Thus, TLR7 plays a critical role in the induction of cross-protective immunity upon vaccination with WIV. The initial target cells for WIV appear to be pDCs which by direct or indirect mechanisms promote activation of robust CTL responses against conserved influenza epitopes.</p>

Preparation and characterization of innovative protein-coated poly(methylmethacrylate) core-shell nanoparticles for vaccine purposes

This study aims at developing novel core-shell poly(methylmethacrylate) (PMMA) nanoparticles as a delivery system for protein vaccine candidates. Materials and Methods. Anionic nanoparticles consisting of a core of PMMA and a shell deriving from Eudragit L100/55 were prepared by an innovative synthetic method based on emulsion polymerization. The formed nanoparticles were characterized for size, surface charge and ability to reversibly bind two basic model proteins (Lysozyme, Trypsin) and a vaccine relevant antigen (HIV-1 Tat), by means of cell-free studies. Their in vitro toxicity and capability to preserve the biological activity of the HIV-1 Tat protein were studied in cell culture systems. Finally, their safety and immunogenicity were investigated in the mouse model. Results. The nanoparticles had smooth surface, spherical shape and uniform size distribution with a mean diameter of 220 nm. The shell is characterized by covalently bound carboxyl groups negatively charged at physiological pH, able to reversibly adsorb large amounts (up to 20% w/w) of basic proteins (Lysozyme, Trypsin and HIV-1 Tat), mainly through specific electrostatic interactions. The nanoparticles were stable, not toxic to the cells, protected the HIV-1 Tat protein from oxidation, thus preserving its biological activity and increasing its shelf-life, and efficiently delivered and released it intracellularly. In vivo experiments showed that they are well tolerated and elicit strong immune responses against the delivered antigen in mice. Conclusions. This study demonstrates that these new nanoparticles provide a versatile platform for protein surface adsorption and a promising delivery system particularly when the maintenance of the biologically active conformation is required for vaccine efficacy