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Many vaccines make use of an adjuvant to achieve stronger immune responses. Alternatively, potent immune responses have also been generated by replacing the standard needle and syringe (which places vaccine into muscle) with devices that deliver vaccine antigen to the skin's abundant immune cell population. However it is not known if the co-delivery of antigen plus adjuvant directly to thousands of skin immune cells generates a synergistic improvement of immune responses. In this paper, we investigate this idea, by testing if Nanopatch delivery of vaccine - both the antigen and the adjuvant - enhances immunogenicity, compared to intramuscular injection. As a test-case, we selected a commercial influenza vaccine as the antigen (Fluvax 2008®) and the saponin Quil-A as the adjuvant. We found, after vaccinating mice, that anti-influenza IgG antibody and haemagglutinin inhibition assay titre response induced by the Nanopatch (with delivered dose of 6.5ng of vaccine and 1.4μg of Quil-A) were equivalent to that of the conventional intramuscular injection using needle and syringe (6000ng of vaccine injected without adjuvant). Furthermore, a similar level of antigen dose sparing (up to 900 fold) - with equivalent haemagglutinin inhibition assay titre responses - was also achieved by delivering both antigen and adjuvant (1.4μg of Quil-A) to skin (using Nanopatches) instead of muscle (intramuscular injection). Collectively, the unprecedented 900 fold antigen dose sparing demonstrates the synergistic improvement to vaccines by co-delivery of both antigen and adjuvant directly to skin immune cells. Successfully extending these findings to humans with a practical delivery device - like the Nanopatch - could have a huge impact on improving vaccines., (Copyright © 2012 Elsevier B.V. All rights reserved.)

A rapid time to peak serum antibody response following vaccination is particularly important for influenza: the time window between the availability of appropriate antigen and the start of the seasonal epidemic is very short. In this paper, influenza vaccine was delivered to both the epidermis and dermis of mouse skin using densely packed microprojection arrays for vaccination. We found that, after vaccination, around 75% and 90% of the delivered influenza vaccine migrated away from the ear skin within just 2 days and 1 week - respectively. And the time to peak serum antibody response was as early as 2 weeks. This result matches the kinetics achieved by intramuscular injection of liquid vaccine to muscle. Thus, we demonstrate that skin delivery of small vaccine volumes discretely by thousands of densely packed microprojections neither induces delay in kinetics nor interferes with the long-lasting antibody response; compared to conventional intramuscular injection., (Copyright © 2011 Elsevier B.V. All rights reserved.)