DEVELOPMENT OF A SUBUNIT LAWSONIA INTRACELLULARIS VACCINE

Pigs are susceptible to the bacterium Lawsonia intracellularis (LI), a pathogen of economic concern in the swine industry due to increased husbandry costs that arise from decreased average daily weight gain, increased feed conversion ratio, and mortality in older pigs. Disease in swine vary with age, where young pigs have a chronic infection marked by slower weight gain and mild diarrhea while older animals have an acute disease marked by hemorrhaging, bloody diarrhea, and sudden death. This doctoral thesis aims to develop a subunit LI vaccine to reduce the incidence of disease and improve swine health. Previously, LI proteins targeted by antibodies from vaccinated rabbits were identified and suggested to be appropriate for inclusion in an LI subunit vaccine. Work commenced by further evaluating the immunogenicity of LI proteins when formulated in multivalent vaccines with Emulsigen® and ranking these antigens based on their ability to induce humoral and cell-mediated immune responses and protect against disease. As a result, the most immunogenic proteins – FliC, GroEL, ClpP, and YopN were selected for further study. Next, combinations of administration routes and adjuvants were explored to improve vaccine efficacy and maintain immunogenicity. Commercial adjuvants were selected based on past success in livestock vaccines and the resulting formulations were then administered as either an intradermal or intramuscular vaccine. This led to the identification of two formulations – Montanide 61 + Antigens and Montanide 660 + Antigens – that after intramuscular vaccination both induced strong humoral and cellular immunity. A proof-of concept study was used to assess these formulations to protect against disease. Montanide 660 + Antigens reduced the number of bacteria in feces, an important parameter in reducing transmission, while Montanide 61 + Antigens reduced the severity of the disease as assessed by significantly decreased lesions and improved average daily weight gain. To gain knowledge about the type of immune response generated in response to the vaccine and its implications for protection, we clarified the IgG isotype and determined that pigs immunized with Montanide 61 + Antigens induced a stronger IgG2 profile but a more balanced response was observed in the Montanide 660 + Antigens group. Further, when measuring antibody avidity of the Montanide 61 + Antigens sera, GroEL and YopN antibodies had better antibody avidity than FliC antibodies. Thus, antibody isotyping and avidity can be utilized to further drive informed vaccine development choices. The outcome of this work has produced a promising new vaccine for LI that has the potential to benefit animals and producers alike.

Name thesis:degree_name

Doctor of Philosophy (Ph.D.)

Level thesis:degree_level

Doctoral

Discipline thesis:degree_discipline

Veterinary Microbiology

Grantor

University of Saskatchewan

Year dc:date.issued

2025

Author dc:creator

• Fourie, Kezia

Advisor dc:contributor.advisor

• Wilson, Heather

Committee members dc:contributor.committeemember

• Rubin, Joseph
• Costa, Matheus
• Koester, Wolfgang
• Ruzzini, Antonio
• Hope, Jayne
• White, Aaron

• Swine, Vaccines, Bacteria, Lawsonia intracelluaris

Language dc:language.iso

en

Handle dc:identifier.uri

https://hdl.handle.net/10388/16780

OAI identifier oai:identifier

oai:harvest.usask.ca:10388/16780