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.
Highlights
The overall success of a vaccination campaign is measured by the protective efficacy of a vaccine and the population coverage achieved
Desirable attributes of a needle-free ‘patch’ for vaccine delivery include: (1) a small size for ease of distribution; (2) simple and accurate administration; (3) projections sharp enough to penetrate through the stratum corneum, though; (4) short enough not to stimulate dermal pain receptors or pose a waste disposal problem; (5) a simple vaccine-loading procedure without requirement for denaturing temperatures or changes in pH; (6) efficient release of coated material into the skin; and (7) stability of coated vaccine patches at high temperatures over time
The present study aimed to investigate the utility of microprojection patches for the delivery of liveChAd63 and MVA viral vectors encoding the malaria antigens ME-TRAP (Multiple Epitope string fused to Plasmodium falciparum TRAP) and PbCSP (Plasmodium berghei circumsporozoite protein) [24,25]
Summary
The overall success of a vaccination campaign is measured by the protective efficacy of a vaccine and the population coverage achieved. One of the factors limiting access to most licensed vaccines is the requirement for their delivery by hypodermic needles. Since candidate malaria vaccines have indicated only modest levels of protective efficacy in clinical trials to date [2], the number of individuals with direct access to a future vaccine must be high in order to achieve herd immunity. Removing the barriers to vaccine access, such as the requirement for needle delivery, is expected to improve vaccine distribution and uptake. Desirable attributes of a needle-free ‘patch’ for vaccine delivery include: (1) a small size for ease of distribution; (2) simple and accurate administration; (3) projections sharp enough to penetrate through the stratum corneum, though; (4) short enough not to stimulate dermal pain receptors or pose a waste disposal problem; (5) a simple vaccine-loading procedure without requirement for denaturing temperatures or changes in pH; (6) efficient release of coated material into the skin; and (7) stability of coated vaccine patches at high temperatures over time. The Nanopatch was designed with these desirables in mind, with the aim of circumventing current logistical challenges presented by needle delivery of liquid vaccine
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