ABSTRACT
Plant-virus-based vaccines have emerged as a promising avenue in vaccine development. This report describes the engineering of an innovative vaccine platform using the papaya mosaic virus (PapMV) capsid protein (CP) as a carrier protein and a C-terminal fused hepatitis C virus (HCV) E2 epitope as the immunogenic target. Two antigen organizations of the PapMV-based vaccines were tested: a virus-like-particle (VLP; PapMVCP-E2) and a monomeric form (PapMVCP(27-215)-E2). While the two forms of the vaccine were both shown to be actively internalized in vitro in bone-marrow-derived antigen presenting cells (APCs), immunogenicity was demonstrated to be strongly dependent on antigen organization. Indeed, C3H/HeJ mice injected twice with the multimeric VLP vaccine showed a long-lasting humoral response (more than 120 days) against both the CP and the fused HCV E2 epitope. The antibody profile (production of IgG1, IgG2a, IgG2b, IgG3) suggests a Th1/Th2 response. Immunogenicity of the PapMV vaccine platform was not observed when the monomer PapMVCP-E2 was injected. These results demonstrate for the first time the potential of the PapMV vaccine platform and the critical function of multimerization in its immunogenicity.
Subject(s)
Carica/virology , Epitopes/immunology , Genetic Engineering , Hepacivirus/immunology , Mosaic Viruses/genetics , Viral Envelope Proteins/immunology , Viral Vaccines/immunology , Animals , Bone Marrow Cells/cytology , Capsid Proteins/genetics , Capsid Proteins/metabolism , Dendritic Cells/cytology , Dendritic Cells/immunology , Hepacivirus/genetics , Hepatitis C Antibodies/immunology , Hepatitis C Antigens/genetics , Hepatitis C Antigens/immunology , Humans , Mice , Mosaic Viruses/physiology , RNA/genetics , Viral Envelope Proteins/genetics , Viral Vaccines/chemistry , Viral Vaccines/geneticsABSTRACT
Duration and location of breaks in time interval production were manipulated in various conditions of stimulus presentation (Experiments 1-4). Produced intervals shortened and then stabilized as break duration lengthened, suggesting that participants used the break as a preparatory period to restart timing as quickly as possible at the end of the break. This interpretation was supported in Experiment 5, in which similar results were obtained with a reaction time response executed at the end of the break. In all experiments, produced intervals lengthened as the break occurred later during the interval. The authors conclude that varying break location and duration reveal, respectively, the influence of attentional time-sharing before the interruption and of preparatory processes taking place during the break.
