Impact of hormonal status on the induction of an immune response in the pig upper reproductive tract

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Our research interests include developing an effective mucosal vaccination platform that works with current husbandry practices to protect pigs against infectious diseases. Because the majority of pigs in Canada are bred using artificial insemination, we speculated that delivering a vaccine into the uterus at the time of breeding may be an attractive immunization route for the industry. We have already confirmed that our intrauterine vaccine formulation does not affect sperm function, it does not affect fertility, and it does not negatively impact piglet birth weight or health, all of which will be critical for acceptance of this route of immunization by the livestock industry. Our research also shows that vaccines administered to the pig uterus can trigger robust antibody-mediated immunity but the mechanism for how this is achieved is not clear as the upper reproductive tract lacks mucosal-associated lymphoid tissue which was thought to be necessary to induce a mucosal immune response. In this Discovery Grant, we will investigate how the uterus can act as an inductive site for immunization. We will vaccinate the pig uterus during estrus (when they are sexually receptive and when the cervix is permissive) and in diestrus (a progesterone-high state when pigs are not sexually receptive). We will monitor antigen movement across the epithelial wall to determine if the hormonal status impacts uterus permeability to the antigen and we will identify the antigen-presenting cells. Further, we will determine if the site of antigen presentation occurs in the draining lymph nodes or within the tissue such as within lymphoid aggregates near the cervix. Finally, we will determine if antigen-specific cell-mediated immunity to the intrauterine vaccine can be induced after multiple immunizations or whether the cell-mediated immune response cannot be readily induced in this tissue. A greater understanding of how and where antigen presentation occurs in the upper reproductive tract and the cells involved will allow us to formulate vaccines that target these cells to promote protective immunity against infectious diseases in pigs. Contingency plans are in place for all aims. Because trainees can contribute to the direction of their research, they will have the opportunity to redirect their focus should this discovery-based research lead to new and unanticipated findings. Intrauterine vaccines may be of tremendous economic benefit to livestock industries that use artificial insemination as a means of breeding. Should the data from livestock show excellent safety and protection against disease, this area of research may evolve in the future to investigate whether intrauterine immunization could benefit women by protecting them against sexually-transmitted infectious diseases.