Projects

Development of a plant expressed, protein-based subunit vaccine against Brucellosis

Topic: Brucellosis , Vaccinology (tools and technologies) , One Health (including food-borne pathogens)

Summary

Brucellosis is an important bacterial disease of livestock and the most common zoonotic
disease. The current vaccines are effective but unsafe, as they result in animal abortions and are
pathogenic to humans. Virus-like particles are being investigated as molecular scaffolds for foreign
antigen presentation to the immune system. Here, we aim to develop a new-generation subunit vaccine by presenting selected Brucella epitopes on the surface of protein-based core-like particles (CLPs). The safety of the plant-expressed CLPs will be tested first in a mouse animal model and subsequently in target animal studies. This study will form the first step in the development of a safe, efficacious and DIVA-compliant subunit vaccine for the prevention of Brucellosis in both animals and humans.

Objectives & Deliverables

The objectives of this this study is as follows:
1. Demonstrate the expression and assembly of chimeric Orbivirus core-like particles (CLPs), presenting Brucella melitensis epitopes, in Nicotiana benthamiana plants.
2. Test safety and efficacy of these CLPs in a mouse model of Brucellosis
3. Test safety and efficacy of the CLPs in a target animal study (sheep)

We aim to deliver a safe and efficacious subunit vaccine against Brucellosis in sheep and, with further animal trials, other cloven-hooved animals. The next step would be test this vaccine candidate in clinical trials to show its efficacy against Brucellosis in humans.

Challenges

This study investigates whether Brucella epitopes, presented on the surface of protein nanoparticles, are able to elicit a protective immune response against Brucella infection in target animals such as sheep. We have previously reported on a single Brucella melitensis T- cell epitope that is able to elicit a protective immune response in a mouse model of Brucellosis (Rutkowska et al., 2024). However, it is unlikely that a single epitope will lead to the sustainable protection required of a vaccine candidate so here we continue our vaccine development by identifying additional Brucella melitensis epitopes that may be included in a multi-epitope vaccine candidate. These additional chimeric CLPs will need to be tested first in a mouse animal model and subsequently in sheep, the target animals. We currently have the technological challenge of not having BSL-3 facilities to do our mouse trials or sheep trials and require funding for these activities. In addition, we require virulent Brucella isolates with which we can challenge the animals.

Rutkowska, D.A.; Du Plessis, L.H.; Suleman, E.; O’Kennedy, M.M.; Thimiri Govinda
Raj, D.B.; Lemmer, Y. Development of a Plant-Expressed Subunit Vaccine against Brucellosis. Microorganisms 2024, 12,1047. https://doi.org/10.3390/microorganisms12061047

Project Source

Principle Investigator(s)

Planned Completion date: 30/11/2029

Effort: €591393 euros

Principal Investigator(s)