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Evaluation of Host-Pathogen Responses and Vaccine Efficacy in Mice
Published on: February 22, 2019
Vaccination with Pasteurella multocida recombinant OmpA induces strong but non-protective and deleterious Th2-type
S Mady Dabo1, Anthony Confer, Marie Montelongo
1Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK 74078-2007, USA. mady.dabo@okstate.edu
Abstract:
Pasteurella multocida OmpA (PmOmpA) belongs to the major and multifunctional Escherichia coli OmpA family of proteins. We have previously reported that the protein is conserved, immunogenic and an adhesin that binds host cells and host cell extracellular matrix molecules [Dabo SM, Confer AW, Quijano-Blas RA. Molecular and immunological characterization of Pasteurella multocida serotype A:3 OmpA: evidence of its role in P. multocida interaction with extracellular matrix molecules. Microb Pathog 2003;35(4):147-157]. In this study, we found that immunization of mice with the recombinant PmOmpA elicited strong Th2-type immune response, characterized by high immunoglobulin G(1) (IgG(1)) antibodies production. Subsequent intraperitoneal homologous challenge of the immunized mice resulted in lack of protection associated with the high IgG(1) titers in anti-rPmOmpA sera. Furthermore, the protection afforded by vaccination with P. multocida OMPs alone was adversely affected by the addition of the rPmOmpA to the vaccine preparations. The results demonstrate that PmOmpA has a detrimental effect on the efficacy of vaccination with OMPs in mice. Targeted inactivation of pmOmpA gene in P. multocida 232 represents a potential mean towards the development of an effective vaccine candidate.
Insights
Pasteurella multocida OmpA (PmOmpA) vaccination in mice induced a detrimental Th2 immune response, hindering vaccine efficacy. Inactivating the pmOmpA gene may lead to a more effective Pasteurella multocida vaccine candidate.
Area of Science:
- Veterinary Microbiology
- Immunology
- Bacterial Pathogenesis
Background:
- Pasteurella multocida outer membrane protein A (PmOmpA) is a conserved, immunogenic adhesin involved in host-pathogen interactions.
- Previous studies established PmOmpA's role in binding host cells and extracellular matrix molecules.
Purpose of the Study:
- To investigate the immunological effects of recombinant PmOmpA (rPmOmpA) immunization in mice.
- To determine the impact of rPmOmpA on the efficacy of Pasteurella multocida outer membrane protein (OMP) vaccines.
Main Methods:
- Mice were immunized with rPmOmpA, and their immune response was characterized by antibody titers (IgG1).
- Immunized mice were challenged with Pasteurella multocida to assess vaccine protection.
- Vaccine efficacy was evaluated by comparing protection rates with and without rPmOmpA in OMP vaccine preparations.
Main Results:
- rPmOmpA immunization elicited a strong Th2-type immune response, marked by high immunoglobulin G1 (IgG1) antibody production.
- Mice immunized with rPmOmpA showed a lack of protection upon homologous challenge, correlating with high IgG1 titers.
- The addition of rPmOmpA to P. multocida OMP vaccines adversely affected protection in mice.
Conclusions:
- PmOmpA has a detrimental effect on the efficacy of P. multocida OMP vaccination in a mouse model.
- Targeted inactivation of the pmOmpA gene in P. multocida is a promising strategy for developing effective vaccine candidates.
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