When it comes to livestock, foot and mouth disease virus (FMDV) is one of the most devastating picornavirus on the planet, according to the U.S. Department of Homeland Security Science & Technology Directorate (S&T), which recently filed a patent application titled “Modified Picornavirus 3C Proteases and Methods Thereof” with the World Intellectual Property Organization (WIPO).

S&T inventors Dr. John Neilan and Dr. Michael Puckette at the Plum Island Animal Disease Center (PIADC) also have also been involved in a breakthrough related to detection of African Swine Fever in pigs, S&T said in an announcement.

FMD is a serious and economically devastating livestock disease. Foot and mouth disease virus (FMDV) is extremely contagious and afflicts animals with cloven hooves like cows, pigs, sheep and deer, S&T said.

PIADC breakthrough

While FMD vaccines have been commercially produced and used since the mid-1960s, S&T said there are significant issues with them.

First, FMD vaccine manufacturing is historically based on injecting inactivated (dead) FMDV into livestock. Since the U.S. has been an FMD-free country for almost 100 years, by law these FMD vaccines are prohibited from being produced on the U.S. mainland.

“Manufacturing of FMDV prior to its inactivation carries the risk of accidental release if proper biosafety procedures are not followed,” said Puckette, the project leader and a microbiologist at PIADC. “It also carries the risk of an accidental outbreak if there are errors in the manufacturing procedure.”

The new technology invented by Neilan and Puckette could allow FMD vaccine manufacturing in the U.S. because it does not require the use of live FMDV for vaccine production, S&T said.

The PIADC team used synthetic biology to alter and fuse multiple parts of the FMDV genome together to create a vaccine that only uses a portion of the virus genome, instead of a full, live virus.

The entire process is driven by a unique “modified picornavirus 3C protease.” The modified 3C protease cuts up the different parts of the virus to produce an “FMDV-like” particle, S&T said. When the assembled virus-like particles are administered to livestock as a vaccine, they are able to trick the livestock’s immune system into thinking it has been infected by a real live FMDV, but without triggering sickness or destroying the host cells. The animals then develop protective immunity against the FMDV in case they are exposed in the future.

Since none of the vaccine components are extracted from viable virus, it is free from the risks associated with inactivated virus vaccines, S&T said. This is a much safer process for making FMD vaccine, so the U.S. would be allowed to manufacture the vaccine. This significantly improves the capability to protect the U.S. from a catastrophic FMD outbreak, according to S&T.

The novel vaccine technology allows for faster development times and less expensive manufacturing processes.

“A key driver of vaccines, especially livestock vaccines, is cost,” said Neilan, S&T science director at PIADC. “More efficient vaccine manufacturing translates into lower costs, making newer vaccine technologies economically viable.”

Prevention and mitigation of FMD through vaccination has proven extremely difficult because picornaviruses — like FMDV — evolve and mutate frequently, S&T said. Current vaccinations may only be effective for a specific strain or within a specific region.

Using the traditional FMDV vaccine approach, creating new vaccines to combat emerging strains can take years and involve significant expenses. Using synthetic biology, and PIADC’s newly invented technology, FMD vaccines against emerging strains may be completed in only a matter of months, S&T noted.

DIVA compatible

Another consideration in FMD prevention has been that blood-based antibody tests cannot distinguish livestock that has been vaccinated with traditional vaccines from those infected with the virus, which means that if a herd has been vaccinated with a traditionally made FMD vaccine, the World Trade Organization will still prohibit export of that country’s livestock and livestock products due to this inability to differentiate vaccinated from infected animals, S&T said.

Until now. Neilan said by following the PIADC molecular FMD vaccine process, “the new vaccine is DIVA (differentiation of infected from vaccinated animals) compatible.” That means that through a simple blood test, it can also be determined if an animal’s antibodies were from exposure to infectious FMDV or just vaccination. This allows for the potential preservation of healthy, uninfected livestock in the event of an outbreak.

Patent-pending

Like most major accomplishments, the development of this patent-pending invention was a scientific team effort. More than a dozen team members worked on the project for five years. When completed, the DHS Office of General Counsel’s Intellectual Property Division drafted and filed an international patent application under the Patent Cooperation Treaty.

“This technology allows for the more efficient development and manufacturing of vaccines against novel emerging FMDV serotypes,” Neilan said. The invention itself is not for new FMD vaccines, but rather for a new “process” (like a blueprint) for making molecular-based vaccines. By following this newly invented blueprint, other scientists may be able to create future animal and human vaccines, specifically for picornaviruses.

Puckette added, “Following these DHS blueprints, designer vaccines for effective protection against novel, emerging FMDV strains can be developed in months as opposed to years." Thus, the DHS vaccine production process is safer, less expensive and can yield a vaccine stockpile that is more effective against a broader range of FMDV strains.

Going forward, S&T said the goal is to ensure that the DHS FMD vaccine technology is commercialized and made available to protect the agricultural community. The DHS manufacturing blueprints described in the WIPO publication, together with the existing portfolio of five other FMD-related patents, may help to create the next generation of FMD vaccines at a lower cost, with less risk, and faster than ever, the agency said in its announcement.