Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/95869
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Type: Journal article
Title: A multiantigenic DNA vaccine that induces broad hepatitis C virus-specific T-Cell responses in mice
Author: Gummow, J.
Li, Y.
Yu, W.
Garrod, T.
Wijesundara, D.
Brennan, A.
Mullick, R.
Voskoboinik, I.
Grubor-Bauk, B.
Gowans, E.
Citation: Journal of Virology, 2015; 89(15):7991-8002
Publisher: American Society for Microbiology
Issue Date: 2015
ISSN: 0022-538X
1098-5514
Editor: Ou, J.
Statement of
Responsibility: 
Jason Gummow, Yanrui Li, Wenbo Yu, Tamsin Garrod, Danushka Wijesundara, Amelia J. Brennan, Ranajoy Mullick, Ilia Voskoboinik, Branka Grubor-Bauk and Eric J. Gowans
Abstract: There are 3 to 4 million new hepatitis C virus (HCV) infections annually around the world, but no vaccine is available. Robust T-cell mediated responses are necessary for effective clearance of the virus, and DNA vaccines result in a cell-mediated bias. Adjuvants are often required for effective vaccination, but during natural lytic viral infections damage-associated molecular patterns (DAMPs) are released, which act as natural adjuvants. Hence, a vaccine that induces cell necrosis and releases DAMPs will result in cell-mediated immunity (CMI), similar to that resulting from natural lytic viral infection. We have generated a DNA vaccine with the ability to elicit strong CMI against the HCV nonstructural (NS) proteins (3, 4A, 4B, and 5B) by encoding a cytolytic protein, perforin (PRF), and the antigens on a single plasmid. We examined the efficacy of the vaccines in C57BL/6 mice, as determined by gamma interferon enzyme-linked immunosorbent spot assay, cell proliferation studies, and intracellular cytokine production. Initially, we showed that encoding the NS4A protein in a vaccine which encoded only NS3 reduced the immunogenicity of NS3, whereas including PRF increased NS3 immunogenicity. In contrast, the inclusion of NS4A increased the immunogenicity of the NS3, NS4B, andNS5B proteins, when encoded in a DNA vaccine that also encoded PRF. Finally, vaccines that also encoded PRF elicited similar levels of CMI against each protein after vaccination with DNA encoding NS3, NS4A, NS4B, and NS5B compared to mice vaccinated with DNA encoding only NS3 or NS4B/5B. Thus, we have developed a promising "multiantigen" vaccine that elicits robust CMI.
Keywords: T-Lymphocytes
Animals
Mice, Inbred C57BL
Humans
Mice
Hepacivirus
Hepatitis C
Vaccines, DNA
Viral Nonstructural Proteins
Viral Hepatitis Vaccines
Antibodies, Viral
Immunization
Immunity, Cellular
Female
Male
Rights: © 2015, American Society for Microbiology. All Rights Reserved.
DOI: 10.1128/JVI.00803-15
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