Developing a PmSLP3-based vaccine formulation that provides robust long-lasting protection against hemorrhagic septicemia-causing serogroup B and E strains of Pasteurella multocida in cattle

Front Immunol. 2024 May 21:15:1392681. doi: 10.3389/fimmu.2024.1392681. eCollection 2024.

Abstract

Background: Pasteurella multocida is a bacterial pathogen that causes a variety of infections across diverse animal species, with one of the most devastating associated diseases being hemorrhagic septicemia. Outbreaks of hemorrhagic septicemia in cattle and buffaloes are marked by rapid progression and high mortality. These infections have particularly harmful socio-economic impacts on small holder farmers in Africa and Asia who are heavily reliant on a small number of animals kept as a means of subsistence for milk and draft power purposes. A novel vaccine target, PmSLP-3, has been identified on the surface of hemorrhagic septicemia-associated strains of P. multocida and was previously shown to elicit robust protection in cattle against lethal challenge with a serogroup B strain.

Methods: Here, we further investigate the protective efficacy of this surface lipoprotein, including evaluating the immunogenicity and protection upon formulation with a variety of adjuvants in both mice and cattle.

Results: PmSLP-3 formulated with Montanide ISA 61 elicited the highest level of serum and mucosal IgG, elicited long-lasting serum antibodies, and was fully protective against serogroup B challenge. Studies were then performed to identify the minimum number of doses required and the needed protein quantity to maintain protection. Duration studies were performed in cattle, demonstrating sustained serum IgG titres for 3 years after two doses of vaccine and full protection against lethal serogroup B challenge at 7 months after a single vaccine dose. Finally, a serogroup E challenge study was performed, demonstrating that PmSLP-3 vaccine can provide protection against challenge by the two serogroups responsible for hemorrhagic septicemia.

Conclusion: Together, these data indicate that PmSLP-3 formulated with Montanide ISA 61 is an immunogenic and protective vaccine against hemorrhagic septicemia-causing P. multocida strains in cattle.

Keywords: Pasteurella multocida; gram-negative; hemorrhagic septicemia; surface lipoprotein; vaccine.

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Animals
  • Antibodies, Bacterial* / blood
  • Antibodies, Bacterial* / immunology
  • Bacterial Vaccines* / administration & dosage
  • Bacterial Vaccines* / immunology
  • Cattle
  • Cattle Diseases* / immunology
  • Cattle Diseases* / microbiology
  • Cattle Diseases* / prevention & control
  • Female
  • Hemorrhagic Septicemia* / immunology
  • Hemorrhagic Septicemia* / microbiology
  • Hemorrhagic Septicemia* / prevention & control
  • Hemorrhagic Septicemia* / veterinary
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Mice
  • Mice, Inbred BALB C
  • Pasteurella Infections / immunology
  • Pasteurella Infections / microbiology
  • Pasteurella Infections / prevention & control
  • Pasteurella Infections / veterinary
  • Pasteurella multocida* / immunology
  • Serogroup
  • Vaccination

Substances

  • Bacterial Vaccines
  • Antibodies, Bacterial
  • Adjuvants, Immunologic
  • Immunoglobulin G

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was supported by equipment purchase in part by Canada Foundation for Innovation (CFI) and operating funds provided by the Natural Sciences and Engineering Research Council of Canada (NSERC) to TM (RGPIN-2018-06546) and the International Development Research Centre Livestock Innovation Fund (IDRC-LVIF - 109047) to TM, SG-O, AS, and TT. TM holds a Tier II Canada Research Chair in the Structural Biology of Membrane Proteins and SGO holds a Tier I Canada Research Chair in Infectious Immunopathogenesis. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.