Antibody responses to a quadrivalent Hepatitis C viral-like particle vaccine adjuvanted with Toll-like receptor 2 agonists

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.Dale Christiansen, Linda Earnest-Silveira, Brendon Chua, Irene Boo, Heidi E. Drummer, Branka Grubor-Bauk, Eric J. Gowans, David C. Jackson, and Joseph Torres