Evaluation of lumazine synthase fromBacillus anthracisas a presentation platform for polyvalent antigen display
| Autor: | Nicholas J. Mantis, Yangjie Wei, Michael L. Barta, Prashant Kumar, Greta VanSlyke, David B. Volkin, C. Russell Middaugh, Wendy L. Picking, Neal Whitaker, Newton Wahome |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
biology Chemistry Immunogenicity 02 engineering and technology 021001 nanoscience & nanotechnology biology.organism_classification Biochemistry Molecular biology Epitope Lumazine synthase Bacillus anthracis 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology Ricin Antigen biology.protein 0210 nano-technology Antigen-presenting cell Molecular Biology Linker |
| Zdroj: | Protein Science. 26:2059-2072 |
| ISSN: | 0961-8368 |
| DOI: | 10.1002/pro.3243 |
| Popis: | Polyvalent antigen display is an effective strategy to enhance the immunogenicity of subunit vaccines by clustering them in an array-like manner on a scaffold system. This strategy results in a higher local density of antigens, increased high avidity interactions with B cells and other antigen presenting cells, and therefore a more effective presentation of vaccine antigens. In this study, we used lumazine synthase (LS), an icosahedral symmetry capsid derived from Bacillus anthracis, as a scaffold to present 60 copies of a linear B cell epitope (PB10) from the ricin toxin fused to the C terminus of LS via four different linkers. We then investigated the effects of linker length, linker rigidity and formaldehyde crosslinking on the protein assembly, conformational integrity, thermal stability, in vitro antibody binding, and immunogenicity in mice. Fusion of the PB10 peptide onto LS, with varying linker lengths, did not affect protein assembly, thermal stability or exposure of the epitope, but had a minor impact on protein conformation. Formaldehyde crosslinking considerably improved protein thermal stability with only minor impact on protein conformation. All LS_PB10 constructs, when administered to mice by injection without adjuvant, elicited measurable anti-ricin serum IgG titers, although the titers were not sufficient to confer protection against a 10× lethal dose ricin challenge. This work sheds light on the biophysical properties, immunogenicity and potential feasibility of LS from B. anthracis as a scaffold system for polyvalent antigen display. |
| Databáze: | OpenAIRE |
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