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Type: Journal article
Title: A hepatitis C virus DNA vaccine encoding a secreted, oligomerized form of envelope proteins is highly immunogenic and elicits neutralizing antibodies in vaccinated mice
Author: Masavuli, M.G.
Wijesundara, D.K.
Underwood, A.
Christiansen, D.
Earnest-Silveira, L.
Bull, R.
Torresi, J.
Gowans, E.J.
Grubor-Bauk, B.
Citation: Frontiers in Immunology, 2019; 10(MAY):1-19
Publisher: Frontiers
Issue Date: 2019
ISSN: 1664-3224
Statement of
Makutiro Ghislain Masavuli, Danushka K. Wijesundara, Alexander Underwood, Dale Christiansen, Linda Earnest-Silveira, Rowena Bull, Joseph Torresi, Eric J. Gowans and Branka Grubor-Bauk
Abstract: Hepatitis C virus (HCV) persistently infects approximately 71 million people globally. To prevent infection a vaccine which elicits neutralizing antibodies against the virus envelope proteins (E1/E2) which are required for entry into host cells is desirable. DNA vaccines are cost-effective to manufacture globally and despite recent landmark studies highlighting the therapeutic efficacy of DNA vaccines in humans against cervical cancer, DNA vaccines encoding E1/E2 developed thus far are poorly immunogenic. We now report a novel and highly immunogenic DNA vaccination strategy that incorporates secreted E1 and E2 (sE1 and sE2) into oligomers by fusion with the oligomerization domain of the C4b-binding protein, IMX313P. The FDA approved plasmid, pVax, was used to encode sE1, sE2, or sE1E2 with or without IMX313P, and intradermal prime-boost vaccination studies in BALB/c mice showed that vaccines encoding IMX313P were the most effective in eliciting humoral and cell-mediated immunity against the envelope proteins. Further boosting with recombinant E1E2 proteins but not DNA nor virus-like particles (VLPs) expressing E1E2 increased the immunogenicity of the DNA prime-boost regimen. Nevertheless, the antibodies generated by the homologous DNA prime-boost vaccinations more effectively inhibited the binding of VLPs to target cells and neutralized transduction with HCV pseudoparticles (HCVpp) derived from different genotypes including genotypes 1, 2, 3, 4, 5, and 6. This report provides the first evidence that IMX313P can be used as an adjuvant for E1/E2-based DNA vaccines and represents a translatable approach for the development of a HCV DNA vaccine.
Keywords: DNA vaccine
HCV envelope proteins
hepatitis C vaccine
immune response
liver disease
preventative vaccination
viral hepatitis
Rights: © 2019 Masavuli, Wijesundara, Underwood, Christiansen, Earnest- Silveira, Bull, Torresi, Gowans and Grubor-Bauk. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
DOI: 10.3389/fimmu.2019.01145
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