COVID-19 vaccine platform based on fusion of antigen domain to small hypoimmune scaffold
The Covid-19 pandemic is a major threat to the public health and economies. Effective vaccines based on new technologies represent the main hope to stop it. Recent announcements on vaccine results are very promising however multiple vaccines are needed and the stability of vaccines as well as the apparent attenuation of the response due to the vector (adenoviral) or scaffold immune response may limit the efficiency of vaccination. A new vaccine platform invented by the group led by Prof Jerala, Head of Department of Synthetic Biology and Immunology addresses both issues.
Technology
The novelty is the modification of viral protein antigen domain into self-assembling nanoparticles that resemble viral particles. The vaccine is based on highly stable plasmid DNA, coding for a domain of a viral protein, that triggers the production of antigen in human cells, inducing the formation of antibodies and protective T cells. The Covid-19 vaccine has been tested in the mouse model with high antibody titers, viral neutralization and T cell response and the patent application has been filed and submitted for publication. Further pre-clinical studies are ongoing on the hamster model.
Main advantages
- DNA plasmid delivery enables fast design, safety, low cost of production and high stability, thus no requirement for a cold chain.
- Antigen is based on the RBD domain of the Spike protein that directly interacts with the ACE2 receptor and antibodies therefore can neutralize viral binding, non-neutralizing epitopes of the Spike protein are excluded, some of which led in case of SARS to the antibody dependent enhancement (ADE) complication.
- A new type of nanoparticle has been designed based on the genetic fusion with RBD of the SARS-CoV-2 based on the short 24-residue beta annulus peptide (RBD-bann).
- Immunization with DNA plasmid coding for RBD-bann resulted in >100 fold higher antibody titer than monomeric RBD and superior viral neutralization in comparison to several other scaffolds often used constructs – ferritin, lumazine synthase and foldon
- RBD-bann resulted in production of cytotoxic T lymphocytes and production of ɣIFN by RBD-specific T cells.
- Scaffolds used to construct antigen nanoparticles as ferritin, foldon, lumazine synthase or adenoviral vectors elicit antibodies against the scaffold or vector which decreases the efficiency of the subsequent immunization. In case of RBD-bann there was minimal cross-reactivity against the scaffold. This represents an important advantage of this platform in comparison to other scaffolding platforms, which are currently at the cutting edge of the universal influenza vaccine and vaccines against HIV-I and malaria.
- Also immunization with isolated RBD-bann protein resulted in superior immunogenicity in comparison to monomeric antigen, confirming the universal advantage of this vaccine platform
Fields of use: Biotechnology, Diagnostic tests
Technology Readiness Level: TRL3
Intellectual property: Patent pending
Partner sought: R&D collaboration to further develop the technology, licensing or sell of IP rights.
Next steps needed: Partner search to further development
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