Capitol News

Pathogens that spread between animals and humans are responsible for some of the deadliest infectious diseases in humans, including highly pathogenic avian influenza, malaria, rabies, and tuberculosis.

The U.S. Department of Agriculture has awarded a team of scientists led by Srinand Sreevatsan, associate dean for research and graduate studies in the College of Veterinary Medicine at Michigan State University (MSU), to further develop and test an innovative vaccine and delivery platform to prevent bovine tuberculosis in free-roaming white-tailed deer. Sreevatsan is a professor and the associate dean for research and graduate studies in MSU's College of Veterinary Medicine.

Significantly, the flexibility of the vaccine delivery platform may have a public health impact beyond TB — it can be engineered for any antigen to protect against any infectious agent.

Bovine TB, caused by the bacterium Mycobacterium bovis, is a highly infectious disease that spreads among domestic and wild animals as well as humans. It brings a heavy economic burden and public health threat. Bovine TB is one of the most damaging diseases in agriculture worldwide and affects wildlife from the ubiquitous white-tailed deer in Michigan to the Near Threatened white rhinoceros in South Africa. Increasingly, bovine TB infection is associated with multidrug- and extensively drug-resistant M. bovis.

“Controlling bovine TB in animals with vaccination is a primary approach to preventing or mitigating the spread of a disease across animal populations and into human populations,” Sreevatsan said. “Here in Michigan, the rise in bovine TB-infected deer and cattle herds has led to a state of urgency due to restrictions associated with animal trade and movement.”

The existing vaccine for TB, Bacillus Calmette-Guérin (BCG), does not effectively prevent infection or illness in cattle or other animals, including white-tailed deer — the primary reservoir for the disease in the U.S. The vaccine offers no protection against the spread of the disease.

“There’s a need for a vaccine that can be delivered to deer as well as cattle,” Sreevatsan said. “We require a low-cost vaccine and delivery system that will work with animals in the wild, and one that will actually provide a robust immune response.”

Mucosal vaccines elicit immune responses where most pathogens enter the body — mucosal tissue, which includes gastrointestinal, respiratory, and urogenital tracts. Mucosal tissue provides protection against infection and may mute the spread of an infectious disease from individual to individual. Oral or nasal vaccines cost less than injectable vaccines and more closely mimic natural immunity. Oral vaccines also offer significant benefits, but several factors — including the gut’s inhospitable environment — have inhibited their development.

To vaccinate free-roaming white-tailed deer, the research team has created a mucosal vaccine engineered to survive the intestinal mucosal barrier designed to prevent pathogens from entering the body.

Sreevatsan and his colleagues engineered an oral bovine TB vaccine delivery system using Bacillus subtilis spores, a common probiotic found in soil and gastrointestinal tracts of ruminants like deer as well as humans. The spores survive the gut’s protective mucosal barrier.

This probiotic-based vaccine was first developed by Sreevatsan along with collaborators Srinivas Dhandayuthapani from Texas Tech University Health Sciences Center's Center of Emphasis in Infectious Diseases, and Gireesh Rajashekara at Ohio State University’s Center for Food Animal Health. The pilot project funded by Michigan Alliance for Animal Agriculture yielded data required for a compelling USDA grant proposal.

“Using probiotic spores to deliver antigens is a very exciting development,” Sreevatsan said. “We clone bovine TB antigen encoding genes into Bacillus subtilis genetic machinery so they express those antigens when they make spores.”

This delivery method is akin to nanoparticle delivery systems but importantly resistant to environmental factors like acids in digestive tracts. B. subtilis spores will also survive conditions faced within food bait left out for deer consumption.

The team will further develop and test this vaccine system on white-tailed deer across four contiguous counties in Michigan — currently classified by USDA as not free from bovine TB.

“With this platform we are producing machinery not limited only to bovine TB antigens,” Sreevatsan said. “We’re optimistic about its ability delivering vaccines against any infectious disease.”

This mechanism could help eradicate bovine TB among free-roaming animal reservoirs while having broader impacts; researchers can engineer it delivering influenza antigens towards birds pigs other wildlife susceptible towards highly pathogenic avian influenza strains too.

“A Novel Probiotic-Based Oral Delivery Vaccine For Bovine Tuberculosis” receives funding through USDA’s National Animal Disease Preparedness Response Program alongside preliminary research supported via Michigan Alliance For Animal Agriculture grants.

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