A Novel DNA Vaccine Technology Conveying Protection against a Lethal Herpes Simplex Viral Challenge in Mice

Dutton, Julie L., Li, Bo, Woo, Wai-Ping, Marshak, Joshua O., Xu, Yan, Huang, Meei-Li, Dong, Lichun, Frazer, Ian H. and Koelle, David M. (2013) A Novel DNA Vaccine Technology Conveying Protection against a Lethal Herpes Simplex Viral Challenge in Mice. PloS One, 8 10: e76407.1-e76407.9. doi:10.1371/journal.pone.0076407


Author Dutton, Julie L.
Li, Bo
Woo, Wai-Ping
Marshak, Joshua O.
Xu, Yan
Huang, Meei-Li
Dong, Lichun
Frazer, Ian H.
Koelle, David M.
Title A Novel DNA Vaccine Technology Conveying Protection against a Lethal Herpes Simplex Viral Challenge in Mice
Journal name PloS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2013-10-03
Year available 2013
Sub-type Article (original research)
DOI 10.1371/journal.pone.0076407
Open Access Status DOI
Volume 8
Issue 10
Start page e76407.1
End page e76407.9
Total pages 10
Place of publication San Francisco, CA United States
Publisher Public Library of Science
Collection year 2014
Language eng
Subject 1100 Agricultural and Biological Sciences
1300 Biochemistry, Genetics and Molecular Biology
2700 Medicine
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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
UQ Diamantina Institute Publications
 
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