Dry-Coated Live Viral Vector Vaccines Delivered by Nanopatch Microprojections Retain Long-Term Thermostability and Induce Transgene-Specific T Cell Responses in Mice

Abstract

The disadvantages of needle-based immunisation motivate the development of simple, low cost, needle-free alternatives. Vaccine delivery to cutaneous environments rich in specialised antigen-presenting cells using microprojection patches has practical and immunological advantages over conventional needle delivery. Additionally, stable coating of vaccine onto microprojections removes logistical obstacles presented by the strict requirement for cold-chain storage and distribution of liquid vaccine, or lyophilised vaccine plus diluent. These attributes make these technologies particularly suitable for delivery of vaccines against diseases such as malaria, which exerts its worst effects in countries with poorly-resourced healthcare systems. Live viral vectors including adenoviruses and poxviruses encoding exogenous antigens have shown significant clinical promise as vaccines, due to their ability to generate high numbers of antigen-specific T cells. Here, the simian adenovirus serotype 63 and the poxvirus modified vaccinia Ankara – two vectors under evaluation for the delivery of malaria antigens to humans – were formulated for coating onto Nanopatch microprojections and applied to murine skin. Co-formulation with the stabilising disaccharides trehalose and sucrose protected virions during the dry-coating process. Transgene-specific CD8+ T cell responses following Nanopatch delivery of both vectors were similar to intradermal injection controls after a single immunisation (despite a much lower delivered dose), though MVA boosting of pre-primed responses with Nanopatch was found to be less effective than the ID route. Importantly, disaccharide-stabilised ChAd63 could be stored for 10 weeks at 37°C with less than 1 log10 loss of viability, and retained single-dose immunogenicity after storage. These data support the further development of microprojection patches for the deployment of live vaccines in hot climates.

The contribution of vaccination to global health: past, present and future

“…New adjuvants directed at improving the immune response are being tried and the success of the RTS,S vaccine [31,32] is due in large part to the use of the powerful adjuvant AS01. Better methods of preserving vaccines at ambient temperature are being developed [38] and alternative delivery systems including needle-less devices are being explored [39], both of which could facilitate uptake of vaccines in hard to reach areas. Table 3 indicates some of the organisms that are currently the target of vaccine research; recent and continuing technical advances should make it technically possible to develop effective vaccines against most of these pathogens.…”

An Indian Perspective of Some Recent Developments in Polio, DPT, Zika and Rotavirus Vaccines

“…No cold chain: the formulations used to coat the patches can ensure ambient temperature stability of the vaccine [71] . Temperature stability also introduces the option of distributing vaccines to parts of the world where cold chain infrastructure is unreliable or non-existent [71] . Needle-free: the use of an applicator allows the arrays of Nanopatch microprojections to penetrate through the protective outer layer of the skin to deliver a vaccine.…”

Investigation of cell death caused by the Nanopatch™ and its role in vaccine delivery as a physical immune enhancer

“…trehalose [296,346,347]), it is likely that these changes may require pre-clinical, and clinical device that could affect their translation into humans.…”

“…antigens and plasmids such as sulphur rodamine, Coomassie Blue [280,349], OVA [280,349,350], trivalent split virion influenza [3,280,345,350], HPV [304], West Nile viral plasmid [303], whole Chikungunya virus [303], DNA vaccine encoding for HSV-2-gD2 [306,307], as well as live viral vector malaria vaccine [347] amongst several other antigens.…”

“…Importantly, the coated NPs were shown to be thermo-stable for 6 months at 23 °C with trivalent influenza vaccine as assessed by HI assays [351] while adenovirus (live ChAd63 vaccine) was thermo-stable when formulated with trehalose and sucrose as stability enhancers for up to 10 weeks at 37 °C [347]. Others have reported enhanced stability of trivalent influenza vaccine when formulated with trehalose for 1 month at 4 °C and 25 °C, however this was not seen when stored at 37 °C as assessed by HA activity [346].…”