Immunological responses following administration of a genotype 1a/1b/2/3a quadrivalent HCV VLP vaccine

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Christiansen, D; Earnest-Silveira, L; Chua, B; Meuleman, P; Boo, I; Grubor-Bauk, B; Jackson, DC; Keck, ZY; Foung, SKH; Drummer, HE; ...Date
2018-04-24Source Title
Scientific ReportsPublisher
NATURE PUBLISHING GROUPUniversity of Melbourne Author/s
Torresi, Joseph; Christiansen, Dale; Earnest, Linda; Jackson, David; Chua, Brendon; Drummer, HeidiAffiliation
Microbiology and ImmunologyMetadata
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Christiansen, D., Earnest-Silveira, L., Chua, B., Meuleman, P., Boo, I., Grubor-Bauk, B., Jackson, D. C., Keck, Z. Y., Foung, S. K. H., Drummer, H. E., Gowans, E. J. & Torresi, J. (2018). Immunological responses following administration of a genotype 1a/1b/2/3a quadrivalent HCV VLP vaccine. SCIENTIFIC REPORTS, 8 (1), https://doi.org/10.1038/s41598-018-24762-9.Access Status
Open AccessAbstract
The significant public health problem of Hepatitis C virus (HCV) has been partially addressed with the advent of directly acting antiviral agents (DAAs). However, the development of an effective preventative vaccine would have a significant impact on HCV incidence and would represent a major advance towards controlling and possibly eradicating HCV globally. We previously reported a genotype 1a HCV viral-like particle (VLP) vaccine that produced neutralizing antibodies (NAb) and T cell responses to HCV. To advance this approach, we produced a quadrivalent genotype 1a/1b/2a/3a HCV VLP vaccine to produce broader immune responses. We show that this quadrivalent vaccine produces antibody and NAb responses together with strong T and B cell responses in vaccinated mice. Moreover, selective neutralizing human monoclonal antibodies (HuMAbs) targeting conserved antigenic domain B and D epitopes of the E2 protein bound strongly to the HCV VLPs, suggesting that these critical epitopes are expressed on the surface of the particles. Our findings demonstrate that a quadrivalent HCV VLP based vaccine induces broad humoral and cellular immune responses that will be necessary for protection against HCV. Such a vaccine could provide a substantial addition to highly active antiviral drugs in eliminating HCV.
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