Abstract
Recombinant virus-like particles (VLPs) represent a promising tool for protein engineering. Recently, trichodysplasia spinulosa-associated polyomavirus (TSPyV) viral protein 1 (VP1) was efficiently produced in yeast expression system and shown to self-assemble to VLPs. In the current study, TSPyV VP1 protein was exploited as a carrier for construction of chimeric VLPs harboring selected B and T cell-specific epitopes and evaluated in comparison to hamster polyomavirus VP1 protein. Chimeric VLPs with inserted either hepatitis B virus preS1 epitope DPAFR or a universal T cell-specific epitope AKFVAAWTLKAAA were produced in yeast Saccharomyces cerevisiae. Target epitopes were incorporated either at the HI or BC loop of the VP1 protein. The insertion sites were selected based on molecular models of TSPyV VP1 protein. The surface exposure of the insert positions was confirmed using a collection of monoclonal antibodies raised against the intact TSPyV VP1 protein. All generated chimeric proteins were capable to self-assemble to VLPs, which induced a strong immune response in mice. The chimeric VLPs also activated dendritic cells and T cells as demonstrated by analysis of cell surface markers and cytokine production profiles in spleen cell cultures. In conclusion, TSPyV VP1 protein represents a new potential carrier for construction of chimeric VLPs harboring target epitopes.
Highlights
Viral structural proteins produced in heterologous expression systems and self-assembled to virus-like particles (VLPs) represent promising tools for modern vaccinology and diagnostics
It has been found that the best structural template for modeling both native and recombinant versions of trichodysplasia spinulosa-associated polyomavirus (TSPyV) viral protein 1 (VP1) protein is PDB:1sva–SV40 capsid (HHPRED Prob = 100.0, 56% identical VP1, lowest alignment gaping level)
TSPyV VP1 protein represents a new carrier for insertion of foreign epitopes at surface-exposed positions within the HI or BC loop
Summary
Viral structural proteins produced in heterologous expression systems and self-assembled to virus-like particles (VLPs) represent promising tools for modern vaccinology and diagnostics. VLPs originating from almost all classes of viruses have been evaluated as carriers for generation of chimeric VLPs presenting foreign epitopes or large protein segments. The first reported VLP carrier with inserted foreign epitopes was hepatitis B virus (HBV) core antigen (HBcAg) [4]. The HBcAg-derived chimeric VLPs have been successfully used for presenting HBV preS1 epitope, specific epitopes of hepatitis C virus, dengue virus, Plasmodium falciparum, tumor epitopes [7,8,9,10,11].
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