Office of Technology Transfer – University of Michigan

Production and Engineering of Enveloped Influenza Virus-Like Particles in yeast cells.

Technology #6531

Influenza is a contagious, widespread viral infection that affects the respiratory system. Influenza affects nearly 5 million people and causes 250,000 to 500,000 deaths annually. The virus mutates rapidly, making it difficult to produce a long-term vaccination and therefore an annual vaccination must be developed. Currently, influenza vaccines are produced mainly using chicken egg-based techniques which is costly and can take up to six months to produce. New techniques are being developed to move away from egg-based techniques including the use of virus like particles (VLPs). VLPs maintain the structure and complexity of the virus it mimics but without the genome present making them non-infectious and safe for vaccinations. The use of VLPs also allows for the expression of more than one protein and strain. This means, all four envelope proteins of influenza can be expressed along with multiple strains. More than two type A strains can be produced in one single vaccination. This new technology presents a way to develop influenza VLPs using yeast cells. This system allows efficient and cost effective production of VLPs that can then be used for a vaccination. Additionally, the system can be adapted to produce and engineer vaccines for other viruses.

Novel Method for Producing Influenza Virus Like Proteins in Yeast Cells

The influenza VLP is produced in yeast by overexpressing the four envelope proteins of influenza. The VLP is assembled at the plasma membrane and then the yeast cell wall is removed allowing for the release of the particles from the spheroplast. These can then be harvested for further use. These particles have been verified and tested in in vitro assays. The production of VLPs from spheroplasts in yeast has been utilized successfully in the production of HIV VLP. The technology herein differs in the ability to express multiple proteins, utilization of inducible promoters, and a differing chemical in the production of the spheroplasts. There are current influenza VLPs produced using insect and plant cells but this technology provides the first influenza VLP produced in yeast. Yeast cut down on production costs and times compared to that of insect and plants due to a shorter growth period. The use of this method could allow for influenza vaccines to protect against more circulating strains. This technology is not only attractive to pharmaceutical companies that produce influenza vaccines but other vaccinations as well.

Applications

  • Production of influenza vaccine
  • Engineering and production of other viral vaccines
  • High-throughput tool to explore host-pathogen interactions and recognition

Advantages

  • Improve R&D efficiency and effectiveness
  • Save production time
  • Decrease costs
  • Reliable large-scale production
  • Multiple strain production in one vaccine
  • Multiple protein expression over just HA protein