Preparation of the Multifunctional Liposome-Containing Microneedle Arrays as an Oral Cavity Mucosal Vaccine Adjuvant-Del
Recently, the multifunctional liposome-constituted microneedle arrays (LiposoMAs) have been proven to be an interesting vaccine adjuvant-delivery system (VADS) that are stable and can be vaccinated via oral cavity mucosal route. When given to mice at oral
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Introduction Mucosal vaccination, namely vaccination at mucosas where numerous mucosa-associated lymphoid tissues (MALT) are located, is convenient and has a good compliance with the vaccinees. Effective mucosal vaccination can not only ignite the body to set up the antigen-specific cellular and humoral immunity but also may elicit the body to engender widespread mucosal immunoresponses to the vaccine antigens, establishing a robust multiple defense against the invading pathogens [1]. To be effective, mucosal vaccines must approach the professional antigen-presenting cells (APCs) to induce potent immunoresponses resulting in plentiful functional pathogen-specific antibodies and cytotoxic T lymphocytes (CTLs) to neutralize and lyse the invaded pathogens, such as HIV and HPV, which once enter the cells can rapidly integrate into the host genome forming a latent reservoir that can hardly be eliminated by conventional antiretroviral agents [2]. Notably, the mucosal vaccines that can block the invasion of various intractable pathogens at the initial entering sites are now in most cases, though desirably needed, still in deficiency and are still difficult to develop due to certain big obstacles. Firstly, the mammal mucosas suitable for vaccination are usually covered with a defending layer of mucus which is continuously renewed and contains various categories of agents, such as antiseptic lysozyme, proteinases, and glycoprotein mucins [3], not only imposing a potential damage to vaccine antigens but also preventing mucosal vaccines from approaching and crossing the epithelial layer, under which the professional APCs are sited. Secondly, the tightly-lined epithelial cells with intercellular spaces sealed by tight junctions
Sunil Thomas (ed.), Vaccine Design: Methods and Protocols, Volume 2: Vaccines for Veterinary Diseases, Methods in Molecular Biology, vol. 1404, DOI 10.1007/978-1-4939-3389-1_42, © Springer Science+Business Media New York 2016
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also form a barrier to mucosal vaccines to reach the professional APCs which are the necessary sponsors for the immunoresponses to the vaccines. Compared to other mucosal sites, oral cavity mucosa confronts a mild environment and is easily accessible, relatively safe for vaccination [4], and also enriched in APCs to mediate innate and adaptive immunoresponses to block local and systemic infections [5]. Unfortunately, oral mucosal immunization is further limited by both its anatomic structure of stratified squamous epithelium (SSE) and the rapid clearance of subjects from mucosal surfaces by flow of saliva, movement of tongue and jaws, and chewing and swallowing [6]. To conquer these barriers to oral mucosal delivery, up to now numerous technologies have been developed [6], with two most common and practical strategies being to incorporate a bioadhesive polymer to the carrier [7] and to use permeation enhancers (e.g., a mucolytic agent of N -acetyl-l -cysteine); however, the paraesthesia caused by bioadhesive leading to saliva supersecretion
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