Immunogenicity of papaya mosaic virus-like particles fused to a hepatitis C virus epitope: evidence for the critical function of multimerization.
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.
Denis
Jérôme
J
Centre de Recherche en Infectiologie, Pavillon CHUL, Université Laval, 2705 boul. Laurier, Québec, PQ, Canada.
Majeau
Nathalie
N
Acosta-Ramirez
Elizabeth
E
Savard
Christian
C
Bedard
Marie-Claude
MC
Simard
Sabrina
S
Lecours
Katia
K
Bolduc
Marilène
M
Pare
Christine
C
Willems
Bernard
B
Shoukry
Naglaa
N
Tessier
Philippe
P
Lacasse
Patrick
P
Lamarre
Alain
A
Lapointe
Réjean
R
Lopez Macias
Constantino
C
Leclerc
Denis
D
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*
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