July 10, 2024


USDA awards grant for innovative bovine TB vaccine development


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


Notably, the flexibility of the vaccine delivery platform may extend beyond TB, as it can be engineered for any antigen to protect against various infectious agents.


Bovine TB, caused by Mycobacterium bovis, is a highly infectious disease affecting domestic and wild animals, as well as humans, resulting in significant economic and public health challenges. The disease is particularly damaging in agriculture worldwide and affects wildlife, from Michigan's white-tailed deer to South Africa's Near Threatened white rhinoceros. Increasingly, bovine TB infection is associated with multidrug and extensively drug-resistant M. bovis.


"Controlling bovine TB in animals through vaccination is a primary approach to preventing or mitigating the spread of the disease across animal populations and into human populations," Sreevatsan stated. In Michigan, the rise in bovine TB-infected deer and cattle herds has created a sense of urgency due to restrictions on animal trade and movement.


The existing TB vaccine, Bacillus Calmette-Guérin (BCG), is ineffective in preventing infection or illness in cattle and other animals, including white-tailed deer, the primary reservoir for the disease in the US. The vaccine does not prevent the spread of the disease.


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


Mucosal vaccines elicit an immune response where most pathogens enter the body - mucosal tissue, including the gastrointestinal, respiratory, and urogenital tracts. Mucosal tissue offers protection against infection and may reduce the spread of infectious diseases from individual to individual. Oral or nasal vaccines are less expensive than injectable vaccines and mimic natural immunity more closely. However, the development of oral vaccines has been hindered by the gut's inhospitable environment.


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


Sreevatsan and his colleagues used Bacillus subtilis spores, a common probiotic found in the environment and the gastrointestinal tract of ruminants and humans, to create the delivery system for the oral bovine TB vaccine. The spores can survive the gut's protective mucosal barrier.


This probiotic-based vaccine was initially developed by Sreevatsan and collaborators, Srinivas Dhandayuthapani from Texas Tech University Health Sciences Centre and Gireesh Rajashekara at Ohio State University's Centre for Food Animal Health. The pilot project, funded by the Michigan Alliance for Animal Agriculture, provided the data required for a compelling USDA grant proposal.


"Using probiotic spores to deliver antigens is a very exciting development," Sreevatsan said. "We clone the bovine TB antigen, encoding genes in the genetic machinery of Bacillus subtilis, and program it to express those antigens when they form spores."


This delivery method is like a nanoparticle delivery system but is more resistant to environmental factors like acids in the digestive tract. The B. subtilis spores will also survive the conditions they will face in the food bait left out for deer to consume.


The team will further develop and test the vaccine and delivery system in white-tailed deer in four contiguous counties in Michigan, the only area in the U.S. not classified as free of bovine TB by the USDA.


"With this platform, we are creating a machinery of specialist suppliers that isn't limited to bovine TB antigens," Sreevatsan said. "We're very optimistic about its ability to deliver vaccines for any infectious disease."


This vaccine delivery mechanism could help eradicate bovine TB in any free-roaming animal that serves as a reservoir for the disease and could have a broader impact. Researchers can engineer it to deliver influenza antigens to birds, pigs, and other wildlife species susceptible to highly pathogenic avian influenza.


"A Novel Probiotic-Based Oral Delivery Vaccine for Bovine Tuberculosis" is funded by USDA's National Animal Disease Preparedness and Response Programme. Preliminary research was funded by a Michigan Alliance for Animal Agriculture grant.


-      MSU Today