Abstract
Adjuvants play a key role in boosting immunogenicity of vaccines, particularly for subunit protein vaccines. In this study we investigated the induction of antibody response against trivalent influenza subunit protein antigen and a saponin adjuvant, QS-21. Clinical trials of QS-21 have demonstrated the safety but, also a need of high dose for optimal immunity, which could possibly reduce patient acceptability. Here, we proposed the use of a skin delivery technology – the Nanopatch – to reduce both adjuvant and antigen dose but also retain its immune stimulating effects when compared to the conventional needle and syringe intramuscular (IM) delivery. We have demonstrated that Nanopatch delivery to skin requires only 1/100th of the IM antigen dose to induce equivalent humoral response. QS-21 enhanced humoral response in both skin and muscle route. Additionally, Nanopatch has demonstrated 30-fold adjuvant QS-21 dose sparing while retaining immune stimulating effects compared to IM. QS-21 induced localised, controlled cell death in the skin, suggesting that the danger signals released from dead cells contributed to the enhanced immunogenicity. Taken together, these findings demonstrated the suitability of reduced dose of QS-21 and the antigen using the Nanopatch to enhance humoral responses, and the potential to increase patient acceptability of QS-21 adjuvant.
Highlights
(e.g. Malaria and Herpes Zoster vaccine) included QS-21 as adjuvant due to its safety profile and the ability to enhance immunogenicity[13,14]
For the first time, the use of a single low QS-21 dose at 1.5 μg delivered to skin by Nanopatches with a licensed influenza subunit antigen induces robust antigen specific IgG responses in a mouse model
A scaled up dose of 50 to 100 μg of QS-21 and 50 μg MPL (AS01/AS02 adjuvant mixtures) were required in human clinical trials to achieve robust immune responses with IM delivery[13,14,16]
Summary
(e.g. Malaria and Herpes Zoster vaccine) included QS-21 as adjuvant due to its safety profile and the ability to enhance immunogenicity[13,14]. Malaria vaccine (with QS-21 as a component of the adjuvant) is currently under review for the regulatory application to European Medicines Agency to be licensed for human use[17,18]. These studies showed the safety and enhanced immunogenicity of QS-21 in IM-based vaccinations. We have shown that our skin delivery device (Nanopatch) successfully generates potent immune responses and dose sparing (compared to IM) with many antigens: including ovalbumin[7,19], trivalent influenza subunit protein (Fluvax)[6,20,21], live viral vector encoding malaria antigen vaccine[22]; and adjuvants such as QA and CpG ODN7, amongst others. This pain could be due to either the high dose of QS-21 (i.e. 50 or 100 μg)[10,14] or the delivery method (i.e. needle and syringe IM delivery)[29,30] or the combination of both
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