DNA vaccine delivery by densely-packed and short microprojection arrays to skin protects against vaginal HSV-2 challenge

ArticleinVaccine 28(47):7483-91 · November 2010with31 Reads
DOI: 10.1016/j.vaccine.2010.09.014 · Source: PubMed
There is an unmet medical need for a prophylactic vaccine against herpes simplex virus (HSV). DNA vaccines and cutaneous vaccination have been tried for many applications, but few reports combine this vaccine composition and administration route. We compared DNA administration using the Nanopatch™, a solid microprojection device coated with vaccine comprised of thousands of short (110 μm) densly-packed projections (70 μm spacing), to standard intramuscular DNA vaccination in a mouse model of vaginal HSV-2 infection. A dose-response relationship was established for immunogenicity and survival in both vaccination routes. Appropriate doses administered by Nanopatch™ were highly immunogenic and enabled mouse survival. Vaginal HSV-2 DNA copy number day 1 post challenge correlated with survival, indicating that vaccine-elicited acquired immune responses can act quickly and locally. Solid, short, densely-packed arrays of microprojections applied to the skin are thus a promising route of administration for DNA vaccines.
    • "Enhanced antibody response to a DNA vaccine using a different antigen delivered by the Nanopatch has also been previously reported by us [22]. Our previous study using an HSV plasmid in BALB/c mice shows very similar antibody pattern with 1 μg vaccine delivered by the Nanopatch to induce a similar response to 10 μg delivered IM and 10 μg delivered by the Nanopatch to be superior to 10 μg delivered IM [22]. These two studies and a microneedle study [13] combine to reinforce the hypothesis that Nanopatch or microneedle delivery is effective in enhancing the immunogenicity of DNA vaccine-encoded antigens to the skin where a high concentration of immunologically active cells reside. "
    [Show abstract] [Hide abstract] ABSTRACT: DNA vaccines have many advantages such as thermostability and the ease and rapidity of manufacture; for example, in an influenza pandemic situation where rapid production of vaccine is essential. However, immunogenicity of DNA vaccines was shown to be poor in humans unless large doses of DNA are used. If a highly efficacious DNA vaccine delivery system could be identified, then DNA vaccines have the potential to displace protein vaccines. In this study, we show in a C57BL/6 mouse model, that the Nanopatch, a microprojection array of high density (> 21,000 projections/cm2), could be used to deliver influenza nucleoprotein DNA vaccine to skin, to generate enhanced antigen specific antibody and CD8+ T cell responses compared to the conventional intramuscular (IM) delivery by the needle and syringe. Antigen specific antibody was measured using ELISA assays of mice vaccinated with a DNA plasmid containing the nucleoprotein gene of influenza type A/WSN/33 (H1N1). Antigen specific CD8+ T cell responses were measured ex-vivo in splenocytes of mice using IFN-γ ELISPOT assays. These results and our previous antibody and CD4+ T cell results using the Nanopatch delivered HSV DNA vaccine indicate that the Nanopatch is an effective delivery system of general utility that could potentially be used in humans to increase the potency of the DNA vaccines.
    Full-text · Article · Jul 2016
    • "The Nanopatch (NP) has a distinctly higher microprojection density than classical microneedle patches: 21,400 cm −2 as compared with <5000 cm −2 [9] . A number of vaccine classes have been successfully dry-coated onto arrays of NP microprojections and dynamically delivered to skin, including split virions101112, protein subunits [13], live viruses [14], plasmid vectors [15,16], and virus-like particles [14]. In mice, only 1/100th of the dose was required to achieve the same functional antihaemagglutinin titres as was induced by IM injection of influenza vaccine [11]. "
    [Show abstract] [Hide abstract] ABSTRACT: Adequate access to effective and affordable vaccines is essential for the prevention of mortality due to infectious disease. Pneumonia - a consequence of Streptococcus pneumoniae infection - is the world's leading cause of death in children aged under 5 years. The development of a needle-free, thermostable pneumococcal-conjugate vaccine (PCV) could revolutionise the field by reducing cold-chain and delivery constraints. Skin patches have been used to deliver a range of vaccines, with some inducing significantly higher vaccine-specific immunogenicity than needle-injected controls in pre-clinical models, though they have yet to be used to deliver a PCV. We dry-coated a licensed PCV onto a microprojection-based patch (the Nanopatch) and delivered it to mouse skin. We analysed resulting anti-polysaccharide IgG responses. With and without adjuvant, anti-polysaccharide IgG titres induced by Nanopatch immunisation were significantly higher than dose-matched intramuscular controls. These improved responses were primarily obtained against pneumococcal serotypes 4 and 14. Importantly, capsule-specific IgG correlated with functionality in an opsonophagocytic killing assay. We demonstrate enhanced anti-PCV immunogenicity when delivered by Nanopatch over intramuscular injection. As the first study of a PCV delivered by a skin vaccination technology, this report indicates the potential for reduced costs and greater global distribution of such a vaccine.
    Full-text · Article · Oct 2015
    • "DNA vaccination against herpes simplex virus-2 (HSV-2) by administration through vaginal mucosa has also been reported [34]. In addition, this study was the report of the DNA vaccination through the vaginal region by using Nanopatch TM in mice systems [34]. These studies suggested that these immunizations are useful for mice against HSV-2 infection or might be effective in HIV infection. "
    [Show abstract] [Hide abstract] ABSTRACT: The advantages of genetic immunization of the new vaccine using plasmid DNAs are multifold. For example, it is easy to generate plasmid DNAs, increase their dose during the manufacturing process, and sterilize them. Furthermore, they can be stored for a long period of time upon stabilization, and their protein encoding sequences can be easily modified by employing various DNA-manipulation techniques. Although DNA vaccinations strongly increase Th1-mediated immune responses in animals, several problems persist. One is about their weak immunogenicity in humans. To overcome this problem, various genetic adjuvants, electroporation, and prime-boost methods have been developed preclinically, which are reviewed here.
    Full-text · Article · Sep 2015
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