Intrauterine immunization – a novel approach to induce mucosal immunity in the reproductive tract

Confocal imaging of immunohistofluorescent staining of rabbit uterus with anti-zonula occludens 1 (αZO1; green) and either anti-Toll-Like receptor 3 (αTLR3; red, left) or a relevant isotype control (right). Nuclei are stained with DAPI (blue). Images by J.A. Pasternak and H.L. Wilson; Pasternak, et. al., (2017), Am J Reprod Immunol 78(5).

Project Team: Heather L. Wilson, Brodie Deluco, Glenn Hamonic, Siew Hon Ng

The uterus is part of the common mucosal immune system, and due to an absence of microbiota, offers a unique site for immunization. The goal of our research is to identify the potential of this approach for application in both humans and livestock. In fact, artificial insemination is a common practice in several livestock species, which offers an opportunity to administer a vaccine at the same time. Using porcine parvovirus as a model disease, we were able to show that intrauterine immunization generated strong antibody responses locally in the uterus and vagina as well as in the blood and nasal passages with just a single administration. This is in stark contrast to commercial vaccines that require multiple immunizations with booster immunizations at each parity. Furthermore, we were able to verify that neither the vaccine antigens nor adjuvants significantly affected sperm function or fertility in pigs. Studies in rabbits confirmed that intrauterine immunization induced robust systemic and mucosal immunity to a multivalent vaccine. Thus, intrauterine immunization may be a critical breakthrough in protecting pigs against porcine parvovirus and other infectious diseases affecting the breeding herd. This may become especially important with the move towards group housing and the increased costs to administer booster immunizations outside gestation stalls. Future research aims at formulating the vaccine to include antigens against Lawsonia intracellularis and Porcine Epidemic Diarrheal Virus antigens to establish a multivalent vaccine.