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

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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 (Hu MAbs) 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.
Keywords
HEPATITIS-C VIRUS, HUMAN MONOCLONAL-ANTIBODIES, INJECTING DRUG-USERS, B-CELL RESPONSES, NEUTRALIZING ANTIBODIES, PARTICLE VACCINE, ANTIVIRAL TREATMENT, E2 GLYCOPROTEIN, ELISPOT ASSAY, INFECTION

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Chicago
Christiansen, D, L Earnest-Silveira, B Chua, Philip Meuleman, I Boo, B Grubor-Bauk, DC Jackson, et al. 2018. “Immunological Responses Following Administration of a Genotype 1a/1b/2/3a Quadrivalent HCV VLP Vaccine.” Scientific Reports 8.
APA
Christiansen, D., Earnest-Silveira, L., Chua, B., Meuleman, P., Boo, I., Grubor-Bauk, B., Jackson, D., et al. (2018). Immunological responses following administration of a genotype 1a/1b/2/3a quadrivalent HCV VLP vaccine. SCIENTIFIC REPORTS, 8.
Vancouver
1.
Christiansen D, Earnest-Silveira L, Chua B, Meuleman P, Boo I, Grubor-Bauk B, et al. Immunological responses following administration of a genotype 1a/1b/2/3a quadrivalent HCV VLP vaccine. SCIENTIFIC REPORTS. 2018;8.
MLA
Christiansen, D, L Earnest-Silveira, B Chua, et al. “Immunological Responses Following Administration of a Genotype 1a/1b/2/3a Quadrivalent HCV VLP Vaccine.” SCIENTIFIC REPORTS 8 (2018): n. pag. Print.
@article{8576090,
  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 (Hu MAbs) 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.},
  articleno    = {6483},
  author       = {Christiansen, D and Earnest-Silveira, L and Chua, B and Meuleman, Philip and Boo, I and Grubor-Bauk, B and Jackson, DC and Keck, ZY and Foung, SKH and Drummer, HE and Gowans, EJ and Torresi, J},
  issn         = {2045-2322},
  journal      = {SCIENTIFIC REPORTS},
  pages        = {13},
  title        = {Immunological responses following administration of a genotype 1a/1b/2/3a quadrivalent HCV VLP vaccine},
  url          = {http://dx.doi.org/10.1038/s41598-018-24762-9},
  volume       = {8},
  year         = {2018},
}

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