hepatitis c vlps delivered to dendritic cells by a tlr2 targeting lipopeptide results in enhanced antibody and cell-mediated responses丙型肝炎种送到树突细胞tlr2瞄准lipopeptide导致增强抗体和细胞介导的反应.pdfVIP

Hepatitis C VLPs Delivered to Dendritic Cells by a TLR2 Targeting Lipopeptide Results in Enhanced Antibody and Cell-Mediated Responses 1 . 2,3. 1 4 1 Brendon Y. Chua * , Douglas Johnson , Amabel Tan , Linda Earnest-Silveira , Toshiki Sekiya , Ruth Chin4, Joseph Torresi2,3, David C. Jackson 1 1 Department of Microbiology and Immunology, The University of Melbourne, Parkville, Victoria, Australia, 2 Department of Infectious Diseases, Austin Hospital, Heidelberg, Victoria, Australia, 3 Department of Medicine, Austin Hospital, The University of Melbourne, Heidelberg, Victoria, Australia, 4 Department of Medicine, Austin Hospital, The University of Melbourne, Heidelberg, Victoria, Australia Abstract Although many studies provide strong evidence supporting the development of HCV virus-like particle (VLP)-based vaccines, the fact that heterologous viral vectors and/or multiple dosing regimes are required to induce protective immunity indicates that it is necessary to improve their immunogenicity. In this study, we have evaluated the use of an anionic self-adjuvanting lipopeptide containing the TLR2 agonist Pam Cys (E Pam Cys) to enhance the immunogenicity of 2 8 2 VLPs containing the HCV structural proteins (core, E1 and E2) of genotype 1a. While co-formulation of this lipopeptide with VLPs only resulted in marginal improvements in dendritic cell (DC) uptake, its ability to concomitantly induce DC maturation at very small doses is a feature not observed using VLPs alone or in the presence of an