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A Novel DNA Vaccine Technology Conveying Protection against a Lethal Herpes Simplex Viral Challenge in Mice.
Title | A Novel DNA Vaccine Technology Conveying Protection against a Lethal Herpes Simplex Viral Challenge in Mice. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Authors | Dutton, JL, Li, B, Woo, W-P, Marshak, JO, Xu, Y, Huang, M-L, Dong, L, Frazer, IH, Koelle, DM |
Journal | PLoS One |
Volume | 8 |
Issue | 10 |
Pagination | e76407 |
Date Published | 2013 |
ISSN | 1932-6203 |
Abstract | While there are a number of licensed veterinary DNA vaccines, to date, none have been licensed for use in humans. Here, we demonstrate that a novel technology designed to enhance the immunogenicity of DNA vaccines protects against lethal herpes simplex virus 2 (HSV-2) challenge in a murine model. Polynucleotides were modified by use of a codon optimization algorithm designed to enhance immune responses, and the addition of an ubiquitin-encoding sequence to target the antigen to the proteasome for processing and to enhance cytotoxic T cell responses. We show that a mixture of these codon-optimized ubiquitinated and non-ubiquitinated constructs encoding the same viral envelope protein, glycoprotein D, induced both B and T cell responses, and could protect against lethal viral challenge and reduce ganglionic latency. The optimized vaccines, subcloned into a vector suitable for use in humans, also provided a high level of protection against the establishment of ganglionic latency, an important correlate of HSV reactivation and candidate endpoint for vaccines to proceed to clinical trials. |
DOI | 10.1371/journal.pone.0076407 |
Alternate Journal | PLoS ONE |
PubMed ID | 24098493 |