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.

Nanoparticle Adjuvant Sensing by TLR7 Enhances CD8+ T Cell–Mediated Protection from Listeria Monocytogenes Infection

“…Moreover, similar results were obtained following depletion of BST2-positive cells, which in naive mice, mainly consists of pDCs, the main source of IFN-a. We thus suggest that following immunization with PapMV, pDCs, and most certainly other APCs, as we have shown previously (22,30,35), take up the particles and degrade them in the endosome allowing recognition of the ssRNA by TLR7, which leads to a massive production of IFN-a in a MYD88 and IRF5/7-dependent fashion. Subsequently, IFN-a is detected by various immune cells through IFNAR leading to their activation as observed by an increased expression of activation markers such as CD69, costimulatory molecules like CD86 and MHC proteins, and the production of other immune mediators such as the proinflammatory cytokine IL-6.…”

“…PapMV-specific Ab titers were determined as described previously (30). Results are expressed as an Ab end-point titer, determined when the OD value is 3-fold greater than the background value obtained with a 1:50 dilution of serum from PBS-injected mice.…”

Novel Plant Virus-Based Vaccine Induces Protective Cytotoxic T-Lymphocyte-Mediated Antiviral Immunity through Dendritic Cell Maturation

“…By genetically modifying these viruses, immunogenic peptides can be fused efficiently to the coat protein (CP) and exposed on the surfaces of the assembled plant VLPs. To date, cowpea mosaic virus, tobacco mosaic virus, alfalfa mosaic virus, potato virus C, tomato bushy stunt virus, zucchini yellow mosaic virus, and plum pox virus are all examples of plant viruses that have been produced successfully and used for the presentation of murine and human epitopes (6,7,22).…”

Adjuvanted influenza vaccines

“…69 They are used as an epitope display system that leads to the production of antibodies against surfaceexposed peptides, thus providing protection. 70,71 Savard et al treated mice and ferrets with PaPMV nanoparticles and observed an increase in the global humoral response to TIV by measuring the increase in total IgG titers, particularly those of the IgG2a subclass. 72 This seems to be important because IgG2a is more effective in preventing intracellular virus replication as it more efficiently activates complement activation and antibody-dependent cell immunity.…”