**Ashish C. Shrestha \*, Danushka K. Wijesundara, Makutiro G. Masavuli, Zelalem A. Mekonnen, Eric J. Gowans and Branka Grubor-Bauk \***

Virology Laboratory, Discipline of Surgery, Basil Hetzel Institute for Translational Health Research and University of Adelaide, Adelaide 5011, Australia; danushka.wijesundara@adelaide.edu.au (D.K.W.); makutiro.masavuli@adelaide.edu.au (M.G.M.); zelalem.mekonnen@adelaide.edu.au (Z.A.M.); eric.gowans@adelaide.edu.au (E.J.G.)

**\*** Correspondence: ashish.shrestha@adelaide.edu.au (A.C.S.); branka.grubor@adelaide.edu.au (B.G.-B.); Tel.: +61-8-8222-6590 (A.C.S.); +61-8-8222-7368 (B.G.-B.)

Received: 8 March 2019; Accepted: 25 April 2019; Published: 30 April 2019

**Abstract:** DNA vaccines present one of the most cost-effective platforms to develop global vaccines, which have been tested for nearly three decades in preclinical and clinical settings with some success in the clinic. However, one of the major challenges for the development of DNA vaccines is their poor immunogenicity in humans, which has led to refinements in DNA delivery, dosage in prime/boost regimens and the inclusion of adjuvants to enhance their immunogenicity. In this review, we focus on adjuvants that can enhance the immunogenicity of DNA encoded antigens and highlight the development of a novel cytolytic DNA platform encoding a truncated mouse perforin. The application of this innovative DNA technology has considerable potential in the development of effective vaccines.

**Keywords:** DNA vaccine; adjuvants; vaccine delivery; plasmid; cytolytic; perforin; bicistronic; HCV; HIV
