Antibody Responses to a Quadrivalent Hepatitis C Viral-Like Particle Vaccine Adjuvanted with Toll-Like Receptor 2 Agonists

Viral Immunol. 2018 May;31(4):338-343. doi: 10.1089/vim.2017.0182. Epub 2018 Feb 28.

Abstract

The development of an effective preventative hepatitis C virus (HCV) vaccine will reside, in part, in its ability to elicit neutralizing antibodies (NAbs). We previously reported a genotype 1a HCV virus like particle (VLP) vaccine that produced HCV specific NAb and T cell responses that were substantially enhanced by Toll-like receptor 2 (TLR2) agonists. We have now produced a quadrivalent genotype 1a/1b/2a/3a HCV VLP vaccine and tested the ability of two TLR2 agonists, R4Pam2Cys and E8Pam2Cys, to stimulate the production of NAb. We now show that our vaccine with R4Pam2Cys or E8Pam2Cys produces strong antibody and NAb responses in vaccinated mice after just two doses. Total antibody titers were higher in mice inoculated with vaccine plus E8Pam2Cys compared to HCV VLPs alone. However, the TLR2 agonists did not result in stronger NAb responses compared to vaccine without adjuvant. Such a vaccine could provide a substantial addition to the overall goal to eliminate HCV.

Keywords: hepatitis C; neutralizing antibody; quadrivalent vaccine; virus-like particles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Animals
  • Antibodies, Neutralizing / blood*
  • Cell Line
  • Disease Models, Animal
  • Hepacivirus / immunology*
  • Hepatitis C / blood
  • Hepatitis C / immunology*
  • Hepatitis C Antibodies / blood*
  • Hepatitis C Antibodies / classification
  • Humans
  • Immunization Schedule
  • Lipopeptides / immunology
  • Mice
  • Mice, Inbred BALB C
  • Neutralization Tests
  • Specific Pathogen-Free Organisms
  • Toll-Like Receptor 2 / agonists
  • Toll-Like Receptor 2 / chemistry*
  • Vaccines, Virus-Like Particle / administration & dosage
  • Vaccines, Virus-Like Particle / immunology*
  • Viral Envelope Proteins / chemistry*
  • Viral Hepatitis Vaccines / administration & dosage
  • Viral Hepatitis Vaccines / immunology

Substances

  • Adjuvants, Immunologic
  • Antibodies, Neutralizing
  • Hepatitis C Antibodies
  • Lipopeptides
  • Toll-Like Receptor 2
  • Vaccines, Virus-Like Particle
  • Viral Envelope Proteins
  • Viral Hepatitis Vaccines