Genetically modified measles viruses are a promising platform for areas such as the development of vector vaccines and oncolytic viruses. A two-component system allows for easier production.
The best protection against measles infection is vaccination with attenuated measles vaccine-strain viruses. Genetically modified measles vaccine-strain viruses are also an interesting platform technology for vector vaccine candidates to protect against other infectious diseases and to potentially treat cancer. Such treatment involves "oncolytic" measles viruses that are specifically intended to kill cancer cells and additionally alert the immune system to attack any remaining cancer cells that have not been killed.
Complex systems have been developed to produce these measles viruses in which the viral replication apparatus is made available via transgenic cell lines and/or additional expression plasmids. These processes require at least four components. They are often inefficient and, due to the many components, complex in terms of adherence to the "Good Manufacturing Practices" (GMPs) required for clinical trials.
Can the process be made easier? Yes, as a research team at the Paul-Ehrlich-Institut has found out. The team was successful in developing a measles virus production system consisting of only two components: the plasmid encoding the (modified) viral genome and a helper plasmid comprising all the required helper functions. This two-component system works when the expression strength – simplified intensity – of the individual components is adapted to the required conditions by means of coordinated control elements (promoters). Promoters are sections of DNA that control the reading (transcription) of a gene (expression). Sophisticated control has made it possible to produce recombinant measles vaccine-strain viruses based on only two plasmids.
The new two-component system does not yet have the efficiency of the more complex systems available thus far. However, these research results pave the way in the long term for testing more efficient methods for the generation of recombinant measles vaccine viruses or vectors and their use in research and development.
We have developed a simplified procedure to produce genetically modified measles viruses that can be useful as a vector vaccine platform and for cancer therapy.
Dr Michael Mühlebach (Head of the "Vectors and Oncolytic Measles Viruses" Research Group and Head of the "Product Testing Immunological Veterinary Medicinal Products" Section)
Auste A, Mühlebach MD (2022): Concentrating all helper protein functions on a single entity allows rescue of recombinant measles virus by transfection of just two plasmids.
J Gen Virol 103: 001815.