Prof. Udo Conrad, Leibniz Institute of Plant Genetics and Crop Plant Research; Dr Hoang Trong Phan, Leibniz Institute of Plant Genetics and Crop Plant Research; Thuong Ho, University of Science and Technology Hanoi
Immunization is an important tool to fight diseases caused by viral, bacterial or fungal pathogenes. There is an ongoing need to develop effective vaccines. Since many pathogens can easily spread from animal hosts to humans – the most prominent example being influenza - it has also to be considered to protect animals by vaccination. Most vaccines can however not be supplied in appropriate quantities in a short time and are too expensive for the application.
The invention provides a new approach for the generation of oligomeric vaccines. The underlying principle is the high affinity interaction between S-protein and S-tag of bovine pancreatic RNase A. Oligomers are generated by co-expression of a modified S-protein and a S-tag fusion protein (for principle see figure 1 in Phan et al. 2017). As example hemagglutinin (H5) was chosen. H5-oligomers were expressed in a transient plant expression system. The obtained high molecular structures show a very high hemagglutination titer. The activity could clearly be related to these structures. It was shown that a specific immune response could be raised in mice after immunization. The oligomeric structures are stable in the plant extract for 1 week at 4° C with no loss of activity.
Oligomeric vaccines have many advantages compared to recently used vaccines. The high molecular structures generated using the described novel approach:
- are highly immunogenic
- are highly stable
- can be applied in the crude extract saving costs and time for downstream processing
- can be produced in a short period of time
- can be applied for broad immunization in veterinary medicine e.g. for poultry having an unlimited scalability.
The proposed technology provides the opportunity to generate oligomeric vaccines for vaccination of human and feedstock.
Patent application pending
Phan H T, Ho T T, Chu H H, Vu T H, Gresch U, Conrad U Neutralizing immune responses induced by oligomeric H5N1-hemagglutinins from plants. Vet. Res. 48 (2017) 53. dx.doi.org/10.1186/s13567-017-0458-x
Fig 1. Hemagglutination titers of plant extracts and inactivated virus rg A/swan/Germany/R65/2006(H5N1). WT: wildtype N. benthamiana; PBS: phosphate buffered saline; S-Protein-mod: modified S-Protein; Fig. 2 Hemagglutination titer of size exclusion chromatography fractions of H5 oligomers and H5-S-Tag (H5-S-Tag with unmodified S-Protein)