Micro-fractional Epidermal Powder Delivery for Skin Vaccination
Skin is a highly immunogenic site for vaccine delivery due to its richness of antigen-presenting cells. Several vaccines have been approved for skin delivery and in particular intradermal delivery in the last two decades. Yet intradermal delivery often ca
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Introduction Vaccination plays a crucial role in global public health. Currently most vaccines are delivered into the muscular tissue, whereas smallpox vaccine, the first successful vaccine in human history was delivered into the skin by scarification [1]. In pursuit of a more potent immune response, there was a renewed interest in exploitation of skin vaccination in the last two decades considering that the skin but not the muscle contains large amounts of antigen-presenting cells [2, 3]. Rabies vaccine is now recommended for intradermal (ID) delivery to address vaccine shortage. Similarly, seasonal influenza vaccine has been approved for ID delivery to save vaccine dose and cost [4–8]. Besides dose sparing, there are also efforts in exploitation of ID delivery to improve vaccine efficacy in the elderly, in which vaccines often induce inferior immune responses due to age-related immunosenescence [9–11]. Despite an improved vaccine immunogenicity, broad application of ID vaccination in the clinics is hampered due to the following reasons. (1) ID vaccination is associated with frequent and sometimes severe local reactions. For example, ID rabies vaccine and seasonal influenza vaccine induce higher rates of local reactions, like erythema, pruritus, edema, as compared to intramuscular (IM) vaccination [4, 6]. Severe local reactions, like ulceration, might breach integrity of the skin and increase local infection risk. Local reactions might also cause skin irritation and affect acceptance of ID vaccination in the clinics. (2) ID vaccination only mildly increases vaccine-induced immune response. Incorporation of adjuvants is long sought after to boost vaccine-induced immune response. Yet they also increase risk of local reactions after ID injection [12–15].
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_46, © Springer Science+Business Media New York 2016
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Due to these reasons, the current ID vaccination contains no external adjuvants and is only approved for delivery of highly immunogenic vaccines that require no adjuvants to be effective. Novel skin delivery technologies capable of minimizing vaccine/ adjuvant-induced local reactions are highly demanded to exploit the full potential of skin vaccination. We recently developed a novel skin delivery technology, called micro-fractional epidermal powder delivery (EPD), for needlefree, painless skin vaccination with minimized local reactions [16]. EPD is based on laser or microneedle treatment to generate microchannel (MC) arrays in the epidermis followed by topical application of powder vaccine-coated array patches to deliver vaccines into the skin via MCs [16]. EPD can efficiently deliver more than 80 % vaccine and adjuvant dose into the skin within 1 h [16]. Interstitial fluid is assumed to play a crucial role in EPD. After laser or microneedle treatment, interstitial fluid would be drawn into each MC and efficientl
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