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

D. Christiansen, L. Earnest-Silveira, B. Chua, P. Meuleman, I. Boo, B. Grubor-Bauk, D. C. Jackson, Z. Y. Keck, S. K.H. Foung, H. E. Drummer, E. J. Gowans, J. Torresi

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Abstract

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.

Original languageEnglish
Article number6483
Number of pages13
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - 24 Apr 2018

Keywords

  • hepatitis C
  • hepatitis C virus

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