Plum Island patent-pending process breakthrough for FMD vaccine

Technology will allow foot-and-mouth disease vaccine manufacturing in the United States because it does not require the use of live FMDV for vaccine production.

June 10, 2020

7 Min Read
Plum Island patent-pending process breakthrough for FMD vaccine
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When it comes to livestock, foot-and-mouth disease is probably the most devastating picornavirus on the planet.

In December of 2019, the World Intellectual Property Organization published a patent application titled "Modified Picornavirus 3C Proteases and Methods Thereof" from Department of Homeland Security Science and Technology Directorate inventors John Neilan and Michael Puckette at the Plum Island Animal Disease Center. These same researchers recently had another breakthrough related to the detection of African swine fever in pigs

FMD is a serious and economically devastating livestock disease. Foot-and-mouth disease virus, the virus causing FMD, is extremely contagious and afflicts animals with cloven hooves like cows, pigs, sheep and deer. It should not be confused with hand-foot-and-mouth disease, which primarily affects humans, especially young children.

When FMD strikes livestock, it causes painful blisters in and around the mouth, nose, mammary glands and hooves. When the blisters burst, they leave raw open wounds that are susceptible to secondary bacterial infections. Along with physical discomfort, the animals experience disinterest in eating and pain when moving, standing and milking. Although the overall FMD mortality rate in adult livestock is relatively low, it can prove fatal for young animals. Survivors are often left in a weakened state and are generally incapable of producing draught-animal power, milk, meat or offspring at the levels they had before infection.

PIADC invention breakthrough
FMD vaccines have been commercially produced and used since the mid-1960s, however there are significant issues with them.

First, FMD vaccine manufacturing is historically based on injecting inactivated (dead) FMDV into livestock. Since the United States 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," says 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 will allow FMD vaccine manufacturing in the United States because it does not require the use of live FMDV for vaccine production. 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" (Protease is an enzyme that catalyzes the breakdown of proteins). The modified 3C protease cuts up the different parts of the virus to produce an "FMDV-like" particle. 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. This is a much safer process for making FMD vaccine, so the United States is allowed to manufacture the vaccine. This significantly improves the capability to protect the United States from a catastrophic FMD outbreak.

The novel vaccine technology allows for faster development times and less expensive manufacturing processes. "A key driver of vaccines, especially livestock vaccines, is cost," says 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. 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.

Finally, an entire country's livestock trade can be embargoed by just one FMD positive test result. A complicating factor 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. This 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.  

Neilan says that 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.

Path to 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," says Neilan. 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 adds, "Following these DHS blueprints, designer vaccines for effective protection against novel, emerging FMDV strains can be developed in months as opposed to year." 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.

Global impact
While FMD has been eradicated in most developed nations this does not mean that FMD-free regions are off the hook as FMD is still prevalent in three-quarters of the countries around the globe. Prevention and monitoring are a constant strain on resources. For countries in the crosshairs of FMD, the toll is high with severe threats to food security, economic prosperity and international livestock trade. Staggering figures cited by the National Institutes of Health estimate the annual number of livestock affected by FMD is between 28 and 79 million animals and the economic losses range between $6.5 billion and $21 billion.

When an FMD outbreak occurs, it can be devastating. The highly communicable virus is directly transmissible from infected animals to susceptible animals, as well as through contaminated materials and products that can harbor infectious virus. It can rapidly blaze through a herd, a region or a country's livestock animals via standard commercial transportation.

The hardships for ranchers, farmers and small landowners can be crushing, both financially and psychologically. When FMD does surface, control of the disease epidemic requires aggressive measures. Infected animals are euthanized. Unfortunately, so are healthy, uninfected animals. Simultaneously, a strict quarantine is enforced, and disinfection protocols are enacted. Over the years, the culling of infected animals (along with healthy ones) has resulted in the slaughter of millions of livestock to protect countries exports from FMD trade bans. This can decimate a nation's agricultural economy and plunge entire populations into immediate food crisis.

Future and FMD
Going forward, 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.

Currently, there is no magic bullet on the horizon for global eradication of FMD, so controlling the spread through any means necessary continues to be the best practice. The researchers say the patent-pending PIADC methodology is the best way to accomplish global control and mitigation.

"I think it has always been my hope to develop something useful, something that makes an actual impact rather than publishing scientific discoveries in a paper that few people will ever read," Puckette says. "I think this work may actually be that and it makes me feel good about the work I and my S&T teammates have done."

Sources: Department of Homeland Security Science and Technology Directorate, which are solely responsible for the information provided, and wholly own the information. Informa Business Media and all its subsidiaries are not responsible for any of the content contained in this information asset.

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