Dengue virus is the most significant disease-causing arbovirus infection in the world. Indeed the World Health Organisation has listed dengue vaccine development as a priority area for the last 40 years, with the increasing numbers and size of epidemics in recent years only highlighting the importance of vaccine availability. Currently there are estimated to be 390 million dengue infections annually leading to 25,000 – 30,000 deaths. Dengue virus is transmitted by the bite of an infected female Aedes aegypti mosquito and may result in anything from an asymptomatic infection through to a range of clinical manifestations, including a self-limiting febrile illness dengue fever (DF) though to the more severe forms of disease, including dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS). The envelope (E) protein contains the majority of antibody neutralizing epitopes present on the virus making it an ideal candidate for a subunit vaccine approach. Truncated recombinant E proteins (sE) of all 4 serotypes of dengue virus were expressed in a Drosophila culture (S2 cells) system and delivered to AG129 mice, with or without Quil A as an adjuvant via subcutaneous (SC), intradermal (ID) injection or via Nanopatch delivery (3 immunizations spaced 4 weeks apart). The Nanopatch contains an ultra high density array (21,025/cm2) of short ~100 μm microprojections. The recombinant proteins are dry coated onto the Nanopatch, and have been shown to be stable, removing the need for a cold chain. With only 10% of the dose used for the SC immunizations, mice immunized with the recombinant protein coated Nanopatch showed >1000 fold increase in IgG titre, enhanced virus neutralization (PRNT80= 1/800) leading to protection from lethal challenge.