The Biodefense and Emerging Diseases Research Meeting, held earlier this week, covered many bioterrorist threats that should be familiar to mBiosphere readers: plague, anthrax, influenza. However, not every biological threat is a mortal threat to humanity. Diseases can disrupt society if enough people become sick, even if the disease doesn’t kill them – imagine the disruption from even a tenth of a city’s population calling in sick: the missing police, teachers, transit workers, cashiers, and doctors would greatly affect the city’s infrastructure (fortunately, we bloggers would be safe). Infrastructure is a prime target for disrupting society.
An important and sometimes overlooked issue of infrastructure is food security. American agriculture and related industries represent $1.5 trillion U.S. dollars and 17% of U.S. jobs. These workers provide the meat, eggs, dairy, and produce that many take for granted will end up on grocery shelves and restaurant menus. Diseases of agriculture represent a real threat to human health, against which scientists and regulatory bodies like the FDA must remain vigilant.
One of these scientists, Dr. Luis Rodriguez of the USDA's Agricultural Research Servise (ARS), focuses on Foot and Mouth Disease Virus, or FMDV, a potentially explosive viral disease of important farm animals such as cattle, pigs, and water buffalo. This Picornavirus is extremely contagious, in part due to its respiratory transmission – once a single animal is infected, the disease will quickly disseminate within a group. The disease is so contagious that Current U.S. law forbids study of FMDV outside of Plum Island – an island research center that can only be reached by ferry.
This law is in place because although FMD was eradicated in the United States in 1929 through massive culling efforts, virus escape from a research center remains a concern. Epidemics can cost billions to control, as the British learned during the 2001 FMD outbreak. There is now an inactivated virus vaccine, but use of this vaccine doesn’t translate well to many parts of the world, where FMDV remains endemic among domesticated and wild animals alike. This is in part because the vaccine needs to match the right viral serotype, of which there are seven. And immunity isn’t lasting – animals need a new shot every 4-6 months to remain protected, which costs $1-2 per animal – an insurmountable cost in some developing countries.
An ideal vaccine would confer lifelong immunity after a single inoculation. It would have a long shelf-life and be composed a stable recombinant viral protein or proteins, circumventing the need to grow large quantities of FMD virus for inactivation and enabling the U.S. to produce its own FMDV vaccines. Creation of a better vaccine is one of the major goals of Rodriguez and his team.
When FMD virus infects a cell, it hijacks the cell’s translational machinery and rapidly begins to produce large amounts of virus. Part of the viral strategy is to use the viral leader protease protein, which cleaves host factor eIF4G, promoting translation of the viral RNA genome. Rodriguez and his team generated a leaderless virus, which is fully attenuated for virulence. An attenuated, live virus could be grown and inoculated into animals without inactivation; many of the most successful viral vaccines have used this strategy. Unfortunately, the leaderless virus is so attenuated “it doesn’t generate enough immune response to protect from wild-type virus,” says Rodriguez. However, strategies using this attenuated virus may allow safe FMDV production in other parts of the U.S., if regulatory hurdles can be crossed.
Vaccines take time to protect animals from disease; in the event of an outbreak, farmers may need a protective measure within 1-2 days, not within the 7 days it takes to build an adaptive immune response. “Foot and mouth disease is like a wildfire,” says Rodriguez. “Ideally, you want something that goes into an animal during an outbreak and confers protection overnight.” To address this problem, Rodriguez and his team are also working to understand ways to activate innate immunity. They’ve identified a biotherapeutic fusion protein, IRF7/3(5D), that can induce prolonged expression of protective interferons and confer short-term protection to exposed animals. Between a potentially improved vaccine and the biotherapeutic, Rodriguez hopes to address short- and long-term protection from FMDV.
These protective measures would allow us to be prepared in the event of an emergency FMD outbreak, which may occur due to malevolent intent. But as recent outbreaks have demonstrated, microbes are often transported by happenstance – globalization allows microbes to travel the world as easily as it does trade goods and people. And the protective measures being studied won’t benefit U.S. agriculture alone
Rodriguez recalls visiting countries where FMDV vaccination is not standard – parts of the Middle East, Africa, Asia, and South America. The FMD effects in those places are very clear, he says. On a recent field excursion to a Uganda, he went to a farm to examine the animals there. “Every single milking cow on the farm had lesions in their teats” due to FMDV infection, he says. These lesions may lead to mastitis, which in turn affect milk production. The impacts on the local farmers, as well as people depending on these cows for food, is tremendous. Rodriguez hopes for a vaccine conferring immunity after a single inoculation to not only protect U.S. agriculture, but to improve agricultural conditions around the world. “Foot-and-mouth disease is a global threat to agriculture,” Rodriguez says.
This work was presented on Wednesday, February 10th, by Luis Rodriguez during the 2016 ASM Biodefense and Emerging Diseasea Research Meeting.
Rodriguez is head of the USDA-ARS Foreign Animal Disease Research Unit at Plum Island. More details on their research can be found at http://www.ars.usda.gov/main/site_main.htm?modecode=80-64-05-05
-- Julie Wolf