The National Veterinary Institute and collaborators developed a Novel Engineered Subunit vaccine against hemorrhagic septicemia of Ruminants that is cross-protective with long lasting protection
The National Veterinary Institute in collaboration of the Universities of Toronto and Calgary has been engaged in the research project on the development of Novel Engineered subunit vaccine against HS since 2019. The research has been conducted with the financial support obtained from an internationally competitive grant secured from International Development Research Center (IDRC) through Livestock Vaccine Innovation Fund (LVIF) programme. The final product of such research is intended to available to low- and middle-income countries (LMIC).
Background:
Hemorrhagic septicemia is an acute and often fatal bacterial disease that affects mainly cattle and buffaloes African and Asian countries. It is caused by a bacterial pathogen, Pasteurella multocida. Most African and Asian countries rank hemorrhagic septicemia as the most important contagious disease in cattle and buffaloes; globally the disease ranks second in terms of livestock units lost for buffalo, and it ranks fifth for cattle. Epidemics due to hemorrhagic septicemia can be economically devastating through its impact on the livelihoods of small holder farmers by significantly reducing animal production, and impeding the harvest of vital crops dependent on animal traction.
Challenges with current vaccines
Vaccination is the most efficient and cost-effective method to control hemorrhagic septicemia. However, currently used inactivated bacterin vaccines are often ineffective because the bacterium has many variants and effective vaccination requires the use of vaccines prepared from each variant. This requires the isolation and identification of each variant (capsular type) as well as knowledge on their distribution for an effective vaccination. This is often complicated by the absence of proper tools to identify these variants. Therefore, the main challenge has been designing vaccines capable of protecting HS caused by all known variants of the bacteria. The other shortcoming , the currently used bacterin vaccine is its low safety record in vaccinated cattle due to occasional occurrence of endotoxic shock which may be fatal in some cases
New approach to develop Innovative protein engineering solution
The research project was carried out jointly by NVI, (Ethiopia), UoT and UoC, (Canada) aimed to isolate and generate novel surface proteins of Pasteurella multocida involved in bacterial iron acquisition system that can potentially confer universal protective immune response, employing innovative approach such as protein engineering. This approach utilized reverse vaccinology to identify genes conserved across all strains of P. multocida causing HS that code for surface proteins potentially involved in bacterial iron acquisition system.
In such an effort that took 5 years, a novel Pasturella multocida surface lipoprotein protein 3 (pmSLP-3) antigen was identified that was formulated into a vaccine. The candidate vaccine was proved to be cross protective with long lasting protection against HS as evidenced by proof-of-concept challenge experiments in cattle. The vaccine is safer and effective for longer duration than the existing commercial vaccines manufactured from whole killed bacteria.
Further process development and optimization for large scale antigen production and formulation is required for commercialization of the candidate vaccine.
The research output has been published in peer reviewed reputable journals which can be accessed through the following links
- Reverse vaccinology-based identification of a novel surface lipoprotein that is an effective vaccine antigen against bovine infections caused by Pasteurella multocida. PLoS Pathog. 2023 Mar; 19(3): e1011249. https://doi.org/10.1371/journal.ppat.1011249
2. 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. https://doi.org/10.3389/fimmu.2024.1392681
Project Leaders and lead researchers
- Professor Anthony B. Schryvers, Department of Biochemistry & Molecular Biology, Cumming School of Medicine, University Calgary, CANADA
- Professor Scott Gray-Owen, Department of Molecular Genetics University of Toronto, CANADA
- Dr Takele Abayneh, National Veterinary Institute, ETHIOPIA