The objective of this project is to develop an oral vaccine delivery system for the immunization of newborn calves. An effective oral vaccine delivery system must be able to protect the vaccine from degradation during passage through the stomach and ensure efficient targeting of the vaccine to the immune system (mucosa-associated lymphoid tissue) in the small intestine. The research in this project involved designing a system to produce solid particles (alginate microspheres) for vaccine delivery and then using these alginate microspheres to formulate vaccine antigens. The efficacy of this vaccine delivery system was then evaluated by delivering oral vaccines to young calves and evaluating specific immune responses to the vaccine antigens.

There were three specific Aims in the project proposal. These Aims were: 1) establish a microsphere production system; 2) target microspheres to the gut-associated lymphoid tissue; and 3) test the efficacy of microspheres for oral vaccine delivery. In the previous reporting periods we completed Aims 1 and 2 and in the present reporting period we addressed Aim 3. In previous reporting periods we established a production unit and standard protocol to produce alginate microspheres. The uptake of alginate microspheres by gut-associated lymphoid tissue (Peyer’s patches) was then established and we then confirmed that uptake of alginate microspheres resulted in the induction of a mucosal immune response in the small intestine.

In the present reporting period we addressed Aim 3 in which we proposed to determine if alginate microspheres provided an effective oral vaccine delivery system for a bovine adenovirus 3 (BAV3) vaccine vector. Experiments performed with intestinal "loops" in young calves revealed that the BAV3 vaccine vector did not induce a vaccine-specific immune response. Therefore, we selected an alternative, commercial rotavirus vaccine antigen (P1P5) and developed a new oral vaccine delivery system. Assays were established to detect P1P5-specific immune responses and P1P5 protein was then expressed using a bacterial expression system. The bacterial expression system induced P1P5-specific immune responses in both the intestinal "loop" model and following oral immunization of young calves. Therefore, this system appears to have significant potential as a commercial oral vaccine delivery system.