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.