title: Immunogenicity of papaya mosaic virus-like particles fused to a hepatitis C virus epitope: evidence for the critical function of multimerization.
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.
authors.affiliation: Centre de Recherche en Infectiologie, Pavillon CHUL, Université Laval, 2705 boul. Laurier, Québec, PQ, Canada.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Denis
authors.forename: Nathalie
authors.initials: N
authors.lastname: Majeau
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Acosta-Ramirez
authors.forename: Christian
authors.initials: C
authors.lastname: Savard
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Bedard
authors.forename: Sabrina
authors.initials: S
authors.lastname: Simard
authors.forename: Katia
authors.initials: K
authors.lastname: Lecours
authors.forename: Marilène
authors.initials: M
authors.lastname: Bolduc
authors.forename: Christine
authors.initials: C
authors.lastname: Pare
authors.forename: Bernard
authors.initials: B
authors.lastname: Willems
authors.forename: Naglaa
authors.initials: N
authors.lastname: Shoukry
authors.forename: Philippe
authors.initials: P
authors.lastname: Tessier
authors.forename: Patrick
authors.initials: P
authors.lastname: Lacasse
authors.forename: Alain
authors.initials: A
authors.lastname: Lamarre
authors.forename: Réjean
authors.initials: R
authors.lastname: Lapointe
authors.forename: Constantino
authors.initials: C
authors.lastname: Lopez Macias
authors.forename: Denis
authors.initials: D
authors.lastname: Leclerc
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D036022:Capsid Proteins / Q000235:genetics / Q000378:metabolism; D029441:Carica / Q000821:virology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D000939:Epitopes / Q000276:immunology*; D005818:Genetic Engineering; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D018937:Hepatitis C Antibodies / Q000276:immunology; D018936:Hepatitis C Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D051379:Mice; D009029:Mosaic Viruses / Q000235:genetics* / Q000502:physiology; D012313:RNA / Q000235:genetics; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*; D014765:Viral Vaccines / Q000737:chemistry / Q000235:genetics / Q000276:immunology*
chemical_list: D036022:Capsid Proteins; D000939:Epitopes; D018937:Hepatitis C Antibodies; D018936:Hepatitis C Antigens; C039919:RNA, recombinant; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C091015:glycoprotein E2, Hepatitis C virus; D012313:RNA