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

• Published in: PloS one Vol. 8; no. 10; p. e76407
• Main Authors: Dutton, Julie L., Li, Bo, Woo, Wai-Ping, Marshak, Joshua O., Xu, Yan, Huang, Meei-li, Dong, Lichun, Frazer, Ian H., Koelle, David M.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 03.10.2013; Public Library of Science (PLoS)
• Subjects: Activation; Analysis; Animal models; Animals; Antibodies, Viral - immunology; Antigens; Antigens, Viral - immunology; Clinical trials; Codon; Codons; Cytotoxicity; Deoxyribonucleic acid; DNA; DNA vaccines; Female; Genomes; Glycoprotein D; Glycoproteins; Herpes simplex; Herpes Simplex - immunology; Herpes Simplex - mortality; Herpes Simplex - prevention & control; Herpes viruses; Herpesvirus 2, Human - genetics; Herpesvirus 2, Human - immunology; Immune response; Immunogenicity; Infections; Infectious diseases; Laboratories; Latency; Lymphocytes; Lymphocytes B; Lymphocytes T; Medical research; Medicine; Melanoma; Mice; Optimization; Plasmids; Polynucleotides; Proteasomes; Proteins; T cells; T-Lymphocyte Subsets - immunology; Technology; Technology application; Ubiquitin; Ubiquitination; Vaccines; Vaccines, DNA - administration & dosage; Vaccines, DNA - immunology; Veterinary medicine; Viral envelope proteins; Viral Envelope Proteins - genetics; Viral Envelope Proteins - immunology; Viral Vaccines - administration & dosage; Viral Vaccines - genetics; Viral Vaccines - immunology; Virology; Viruses; West Nile virus; Queensland Australia; Australia; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0076407

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.