Capsular immunity is necessary for protection against some but not all strains of Glaesserella parasuis

Authors: Hau, Samantha; LUAN, SHI-LU - University Of Cambridge; WEINERT, LUCY - University Of Cambridge; LANGFORD, PAUL - Imperial College; RYCROFT, ANDREW - Royal Veterinary College; WREN, BRENDAN - London School Of Hygiene & Tropical Medicine; MASKELL, DUNCAN - University Of Cambridge; TUCKER, ALEXANDER - University Of Cambridge; BROCKMEIER, SUSAN - Retired ARS Employee

Submitted to: Veterinary Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/7/2025
Publication Date: 4/11/2025
Citation: Hau, S.J., Luan, S., Weinert, L.A., Langford, P.R., Rycroft, A., Wren, B.W., Maskell, D.J., Tucker, A.W., Brockmeier, S. 2025. Capsular immunity is necessary for protection against some but not all strains of Glaesserella parasuis. Veterinary Microbiology. https://doi.org/10.1016/j.vetmic.2025.110509.
DOI: https://doi.org/10.1016/j.vetmic.2025.110509

Interpretive Summary: Glaesserella parasuis (G. parasuis) is a bacterium that causes severe disease in pigs. Death loss can reach 5-10% during outbreaks of disease. G. parasuis is a significant economic burden to swine producers due to the cost of vaccination, treatment, reduced performance, and death loss. G. parasuis isolates produce a carbohydrate capsule. Capsule is an important factor that protects G. parasuis from the host immune system. G. parasuis isolates are grouped into different serotypes based on the type of capsule they produce. There are 15 known G. parasuis serotypes, which complicates G. parasuis control. G. parasuis is controlled with vaccination and antibiotic treatment. Most of the G. parasuis vaccines used by the swine industry are made from killed bacteria. These vaccines can cause immunity specific to the strain or serotype included in the vaccine. If immunity is specific to the vaccine strain, it may not protect against other strains animals are exposed to. We previously generated a strain of G. parasuis that does not produce capsule (capsule mutant). This strain was not able to cause disease in pigs. We hypothesized that using this strain in a vaccine would generate an immune response directed toward proteins rather than capsule that covers or hides surface proteins. Protein directed immunity could provide better cross protection than capsule directed immunity, since it would not be serotype specific. To test this hypothesis, we vaccinated pigs with a vaccine containing killed capsule mutant, killed parent strain, or a mock vaccine. We tested protection against the parent strain (serotype 5) and four other strains (serotype 1, 4, 5, and 13; heterologous challenge). Both vaccines protected against the parent strain and the serotype 1, 4, and 13 strains. However, only vaccination with the parent strain protected against the heterologous serotype 5 strain. We believe this is due to capsule directed immunity. The parent strain produces capsule and the parent strain vaccine would cause an immune response to capsule. The mutant strain would not cause an immune response to capsule because it does not produce capsule. Protection of only animals vaccinated with the parent strain showed capsule immunity was very important for protection against the heterologous serotype 5 strain. We found the heterologous serotype 5 strain produces a large amount of capsule, which would better cover cell surface proteins. The antibodies generated by the capsule mutant vaccine against cell surface proteins were less able to bind to the proteins of the heterologous serotype 5 strain because capsule covers them and were unable to protect pigs from disease. This work shows the importance of strain selection when generating killed vaccines. For many strains, protein directed immunity can protect pigs from disease. However, for strains that produce large amounts of capsule, capsule directed immunity is essential for protection.

Technical Abstract: Glaesserella parasuis is the causative agent of Glässer’s disease in pigs and results in significant losses to the swine industry annually. Due to the serovar and strain specific response associated with many bacterin vaccines, there has been difficulty generating broad heterologous protection. Here, an unencapsulated G. parasuis mutant (HS069'cap) was assessed as a bacterin vaccine and compared to a bacterin made from the encapsulated parent strain, against challenge with the homologous, parent strain (serovar 5) as well as four heterologous challenge strains (serovar 1, 4, 5, and 14). Both the HS069 and HS069'cap bacterins generated high titers to the homologous and heterologous strains. The HS069'cap bacterin was able to provide protection against the parent strain as well as 12939 (serovar 1), 2170B (serovar 4), and MN-H (serovar 13), but was unable to protect animals from challenge with Nagasaki (serovar 5). In contrast, the HS069 bacterin was able to provide protection against all challenge strains, showing the importance of serovar specific immunity against the challenge strain Nagasaki. This appears to be due to the production of a more abundant and well-organized capsule in Nagasaki as compared to HS069. This study indicates HS069'cap is a good candidate strain for bacterin development; however, it may be less able to provide protection against highly encapsulated strains of G. parasuis.