Smallpox DNA vaccine delivered by novel skin electroporation device protects mice against intranasal poxvirus challenge

Previously, we demonstrated that an experimental smallpox DNA vaccine comprised of four vaccinia virus genes (4pox) administered by gene gun elicited protective immunity in mice challenged with vaccinia virus, and in nonhuman primates challenged with monkeypox virus (Hooper JW, et al. Smallpox DNA vaccine protects nonhuman primates against lethal monkeypox. J Virol 2004;78:4433–43). Here, we report that this 4pox DNA vaccine can be efficiently delivered by a novel method involving skin electroporation using plasmid DNA-coated microneedle arrays. Mice vaccinated with the 4pox DNA vaccine mounted robust antibody responses against the four immunogens-of-interest, including neutralizing antibody titers that were greater than those elicited by the traditional live virus vaccine administered by scarification. Moreover, vaccinated mice were completely protected against a lethal (>10LD(50)) intranasal challenge with vaccinia virus strain IHD-J. To our knowledge, this is the first demonstration of a protective immune response being elicited by microneedle-mediated skin electroporation.