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Mesoporous Silicon Microparticles Enhance MHC Class I Cross-Antigen Presentation by Human Dendritic Cells

DOI: 10.1155/2013/362163

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Abstract:

The mesoporous silicon microparticles (MSMPs) are excellent vehicles for releasing molecules inside the cell. The aim of this work was to use MSMPs to deliver viral specific MHC class I restricted epitopes into human antigen presenting cells (monocyte derived dendritic cells, MDDCs) to facilitate their capture, processing, and presentation to CD8+ (cytotoxic) T lymphocytes. We show for the first time that MSMPs vehiculation of antigenic peptides enhances their MHC class I presentation by human MDDCs to CD8 T lymphocytes. 1. Introduction Vaccines in general and virus vaccines in particular are focusing ever more on the induction of cellular immunity, specifically the generation of cytotoxic T lymphocytes (CTLs) [1–4]. Efficiency and safety issues arise with traditional vaccines, consisting of live attenuated or whole inactivated organism, so vaccine design nowadays focuses on the implementation of safer recombinant subunit vaccines [5]. These recombinant subunit antigens require potent adjuvants or immune modulators to enhance their immunogenicity as well as their capacity to trigger CTLs responses required to fend off life-threatening infections caused by intracellular pathogens, such as HIV, malaria, and tuberculosis [6]. The encapsulation of recombinant proteins in biocompatible and biodegradable nano- and microparticles is emerging as a promising approach to boost their immunogenicity by passively targeting them to antigen presenting cells (APCs) [7–9]. By mimicking pathogen dimensions, microparticles are more prone to be phagocyted by APCs than soluble antigen. The most powerful antigen presenting cells are dendritic cells (DCs), which bridge innate and adaptive immunity and are capable of initiating a primary immune response by activating na?ve T cells [10]. The induction of most CD8+ T cell responses by DCs requires the presentation of peptides from internalized antigens by class I major histocompatibility complex (MHC) molecules that usually present endogenous cytoplasmic antigens. This process, essential for the efficacy of therapeutic vaccines, is called cross presentation, and DCs are the main antigen cross presenting and cross priming cell type in vivo [11]. In the last few years the biomedical research field has shown a growing interest in nanostructured silicon materials. Mesoporous silicon microparticles (MSMPs) possess unique chemical and structural properties such as chemical stability, adjustable pore size, extensive surface area, biocompatible and biodegradable nature, and notable cells adherence to its porous surface [12, 13]. These

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