B.FLT.3008-Development of a novel oral vaccine for Bovine Respiratory Disease

Summary

Bovine respiratory disease (BRD) is the leading cause of mortality and morbidity of Australian feedlot cattle. Conventional subcutaneous and intranasal vaccines are important preventatives for the disease, however these delivery platforms have specific cold chain and animal handling requirements.

This project determined whether a yeast-based vaccine platform could improve health by
inducing specific immunity in cattle. This pilot vaccine utilized a ‘reporter’ molecule, ovalbumin, and
assessed immunological parameters and timing of a specific immune response to demonstrate proof
of concept for the vaccine platform. Additionally, BRD virulence-associated epitopes (for Bovine Viral Diarrhoea Virus) were assessed for suitability as candidate antigens, and a yeast vector transformed to express the target antigens.

Whilst the project was successful in obtaining an immune response to 'ovalbumin' reporter molecule in a yeast based vaccine, the project could not successfully transform the yeast based vector to express target antigens for BVDV.

Objectives

This project aimed to:
• evaluate the ability of a yeast-based vaccine that contains a ‘reporter’ to activate cattle immune cells in a laboratory culture system
• assess the ability of the reporter vaccine to induce an immune response in cattle
• deliver a literature review identifying candidate antigens for BRD vaccines and selection of 10-15 ‘best bet’ antigens
• evaluate the ability of the candidate antigens to be recognised by immune cells sourced from BRD infected feedlot cattle
• produce and deliver an oral yeast-based prototype vaccine that contains the candidate BRD antigen/s.

Key findings

• The prototype vaccine (OvaYeast) activated innate immune cells and induced both cellular and antibody responses in cattle
• Yeast is a suitable medium for oral vaccine delivery to cattle as it induced immune responses
• Antibody responses can last for at least 5 months after vaccination
• There is provisional evidence that three candidate BVDV antigens may be antigenic and one has the potential to be immunogenic, however no stably transformed clones of K.lactis yeast expressing these antigens were able to be obtained.

Benefits to industry

The Australian feedlot industry is committed to antimicrobial stewardship and practices that promote animal health and welfare. As such this industry investment reflects the commitment of the industry to investigate new approaches to prevent disease, complement and/or replace antimicrobial use.

MLA action

Currently no further MLA action is planned until it can be demonstrated that development of a viable vaccine containing the immunogenic antigen for BVDV is possible.

Future research

• Further improvements of yeast transformation to optimise use of this K. lactis expression system for production of recombinant antigen vaccine candidates or evaluation of alternate species of yeast.
• Expression of candidate antigens in another expression system (e.g. E. coli) to enable evaluation using other vaccine delivery systems e.g. nanoparticles.
• Further evaluation of yeast vaccine dose and route(s) of administration.
• Evaluation of combining multiple transformed yeasts containing multiple antigens from the major BRD pathogens in a single vaccine, to address the multifactorial nature of this disease.