The objective of this work was to assess a technology’s potential to produce the components of a Foot and Mouth Disease Virus Vaccine which could be (1) differentiated from infected animals (i.e. DIVA vaccine), (2) inexpensively engineered, produced, and distributed to the producers in a matter of days, and (3) engineered to rapidly target the emerging or pandemic strain. Such a vaccine could reduce/eliminate the threat of a $14+ billion dollar loss if a U.S. FMDV outbreak occurred . The technology capable of potentially meeting these objectives is cell-free protein synthesis. Cell-free protein synthesis is the harvesting of protein-making machinery from bacteria and then turning this machinery on in a test tube to make only the desired proteins (in this case, proteins that would make an FMDV vaccine).
2. How research was conducted:
To produce the proteins necessary to make a Foot and Mouth Disease Virus (FMDV) vaccine, we first designed and synthesized only certain genes (DNA) from the FMDV genome. Other genes from FMDV that are necessary to synthesize an infectious virus were not produced. Thus our design enables the production of a DIVA vaccine that would be completely non-infectious. To be certain that the genes necessary for virus infection were not unintentionally produced, the complete FMDV genome was never brought into our lab (only a subset of the genome which was chemically synthesized). Our custom synthetized genes were expressed in our cell-free protein synthesis system to produce the desired proteins. We next assessed for their ability to form a virus-like particle (virus shells that do not contain the virus genome). This virus-like particle is thought to be an effective vaccine. The production system was further optimized by (1) including additional proteins which could help the production of the desired vaccine proteins and (2) varying production conditions.
3. Research findings:
Our research demonstrated for the first time that the FMDV structural proteins could be expressed efficiently using our low-cost cell-free system. We also demonstrated the ability of our cell-free production system to be directly manipulated and optimized for improved production.
4. What these findings mean to the industry:
Our research findings demonstrating the expression of FMDV proteins with our cell-free system are particularly exciting due to the ability of our cell-free system to rapidly produce large quantities of desired proteins. We have thus provided proof-of-concept data establishing the potential of using our cell-free technology for the rapid production of vaccine proteins targeted against an emerging or pandemic FMDV strain. To commercialize this technology, future work includes (1) continued optimization of the production of FMDV vaccine proteins, (2) demonstrating the ability of our cell-free system to be stockpiled and rapidly deployed to produce large quantities of strain-specific FMDV vaccine proteins, and (3) verifying the immunogenicity of the FMDV vaccine proteins.
5. Contact information:
Bradley C. Bundy, Ph.D.
Assistant Professor of Chemical Engineering
Brigham Young University
350S Clyde Building, Provo, UT 84602