Immune responses of cattle vaccinated by various routes with Mycobacterium bovis Bacillus Calmette-Guérin (BCG)

Authors: Palmer, Mitchell; HWANG, SOYOUN - Animal And Plant Health Inspection Service (APHIS); Kanipe, Carly; Putz, Ellie; FERNANDES, LUIS - Oak Ridge Institute For Science And Education (ORISE); DIDKOWSKA, ANNA - Warsaw University Of Life Sciences; Boggiatto, Paola

Submitted to: BMC Veterinary Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/18/2024
Publication Date: N/A
Citation: N/A

Interpretive Summary: Tuberculosis in animals is caused by Mycobacterium bovis, which can also infect humans. The only tuberculosis vaccine available for humans is Mycobacterium bovis strain BCG. BCG has also been evaluated as a possible vaccine for various animals species including wildlife and domestic species. Vaccines for animals, especially wildlife, would likely be administered orally in a vaccine bait. To test the feasibility of different routes of BCG vaccination and different physical states of vaccine (i.e. liquid vs freeze-dried) we evaluated immune responses in calves vaccinated by the subcutaneous route, orally delivered liquid, and orally consumed freeze-dried BCG. Immune responses to BCG were detected in calves receiving BCG subcutaneously and as a liquid delivered to the back of the throat. No detectable responses were seen in calves consuming freeze-dried BCG vaccine. Although freeze-drying is often used to stabilize biological products such as vaccines, incorporating freeze-dried BCG within an oral vaccine bait does not appear to be a viable option. An oral vaccine bait would need to contain liquid BCG.

Technical Abstract: Mycobacterium bovis BCG is the human tuberculosis vaccine and is the oldest vaccine still in use today with over 4 million people vaccinated since 1921. The BCG vaccine has also been investigated experimentally in cattle and wildlife by various routes including oral and SQ. Thus far, oral vaccination studies of cattle have involved liquid BCG or liquid BCG incorporated into a lipid matrix. Lyophilization is an established technique used for stabilizing bioproducts such as vaccines. In the current study, cattle were vaccinated in two phases. In each phase, cattle were divided into four groups. Group 1 received BCG injected SQ, Group 2 received liquid BCG delivered to the posterior oral cavity, Group 3 orally consumed lyophilized BCG contained within a gelatin capsule placed within a small amount of Chaffhaye. Group 4 remained unvaccinated. No vaccinated cattle were positive by an interferon gamma release assay or tuberculin skin testing. An in vitro antigen stimulation assay and flow cytometry were used to detect antigen-specific CD4, CD8 and gamma delta T cell responses following vaccination. Vaccination of animals with oral lyophilized BCG did not result in any increases in the frequency of CD4, CD8 or gamma delta T cell proliferative or IFN-gamma responses at any of the time points analyzed in either phase 1 or 2. In contrast, vaccination with BCG SQ and oral liquid BCG, resulted in an increase in the frequency of proliferating and IFN-gamma-producing CD4 T cells. Responses peaked at 9-12 weeks post-vaccination. Similar to oral lyophilized BCG vaccinated animals, we did not observe any significant increases in the frequency of CD8 and gamma delta T cell proliferative and IFN-gamma responses following SQ or oral liquid vaccinated animals. These data would suggest that vaccination with oral lyophilized BCG does not induce a measurable, antigen-specific cell mediated responses in the periphery, when compared to BCG administered SQ or liquid BCG administered via the oral route. However, vaccination with either SQ or oral liquid BCG does induce measurable CD4 T cell responses in the periphery.