Attenuated herpesvirus-based vaccines for low-cost antibiotic-independent control of bacterial disease in livestock - a proof of concept study

Summary

Headlines are filled with news of drug-resistant bacteria running out of control. The Chief Medical Officer for England highlighted the critical nature of this problem, warning that "antibiotics are losing their effectiveness at a rate that is alarming and irreversible…". There are similar problems in managing bacterial infections in livestock. Overuse in animals may also be increasing resistance in bacteria affecting humans. Vaccination may help tackle the crisis. The Norwegian fishing industry has shown vaccination to be highly effective at controlling bacterial infections without the need for antibiotics. Our aim is to develop an effective vaccine against bovine mastitis (bacterial infection of the udder), a cause of serious health problems in dairy cows. Mastitis also decreases milk production and quality, costing the UK dairy industry £200 million a year. Dairy farmers are making considerable headway in reducing antibiotic usage. Unfortunately, current vaccines against mastitis bacteria are not very effective, which means farmers must still use antibiotics and costly animal management procedures to control mastitis. We will develop a safe and effective vaccine to reduce mastitis in cows using a new kind of vaccine already shown to be effective against other difficult-to-control diseases. This proof-of-concept study will focus on one of the three main bacteria that cause mastitis, Escherichia coli (E. coli). In addition to our main goal of helping UK farmers, a mission of the company leading this project, The Vaccine Group (TVG), is to develop vaccines that also benefit low and middle-income countries (LMICs). Many LMICs, such as Ethiopia, depend on milk for food and mastitis is similarly a big problem. Additional unique selling points of our vaccine therefore relate to its low cost: both in terms of administration, being able to induce long-lived immune responses after only one or two doses, and in regard to vaccine production.

Project outcomes

The Problem: We describe the initial characterization of a new type of vaccine being developed to prevent bacterial infections in agricultural animals without the use of antibiotics. Headlines are filled with news of drug-resistant bacteria running out of control. The Chief Medical Officer for England highlighted the critical nature of this problem, warning that "antibiotics are losing their effectiveness at a rate that is alarming and irreversible…". There are similar problems in managing bacterial infections in livestock. Overuse in animals may also be increasing resistance in bacteria affecting humans. Vaccination may help tackle the crisis. The Norwegian fishing industry has shown vaccination to be highly effective at controlling bacterial infections without the need for antibiotics. 

Our Aim: We will develop an effective vaccine against bovine mastitis (bacterial infection of the udder), a cause of serious health problems in dairy cows. Mastitis also decreases milk production and quality, costing the UK dairy industry £200 million a year. Dairy farmers are making considerable headway in reducing antibiotic usage. Unfortunately, current vaccines against mastitis bacteria are not very effective, which means farmers must still use antibiotics and costly animal management procedures to control mastitis. 

Our Approach: We will develop a safe and effective vaccine to reduce mastitis in cows using a new kind of vaccine already shown to be effective against other difficult-to-control diseases. This proof-of-concept study will focus on one of the three main bacteria that cause mastitis, Escherichia coli (E. coli). In addition to our main goal of helping UK farmers, a mission of the company leading this project, The Vaccine Group (TVG), is to develop vaccines that also benefit low and middle-income countries (LMICs). Many LMICs, such as Ethiopia, depend on milk for food and mastitis is similarly a big problem. Additional unique selling points of our vaccine therefore relate to its low cost: both in terms of administration, being able to induce long-lived immune responses after only one or two doses, and in regard to vaccine production. Results: Results from the present study show that our new vaccine, which expresses a protein of the E. coli bacterium called YncE, can induce an immune response that is able to target the E. coli YncE protein. This immune response was able to recognize the form of YncE that is present within the whole intact bacterium. Together with data from an earlier study showing that immune responses against YncE are protective against E. coli infection, these exciting findings suggest that our vaccine may be able to provide a form of immunity that can prevent E. coli infection. 

Future Work: These promising results from our initial BactiVac-funded pump-priming catalyst award serve as the basis for future work to test whether our vaccine can control E. coli infection in animals. Such a capacity will be a major step towards development of vaccines for antibiotic-free control of mastitis and other bacterial infections in livestock. In the longer term, these discoveries may have direct application towards the use of similar strategies to control human bacterial disease.  


Michael JarvisDr Michael Jarvis
Associate Professor
The Vaccine Group (TVG) Ltd (UK)

Collaborators:
Professor Alain Vanderplasschen, University of Liege (Belgium)

Dr Matthew Upton, University of Plymouth (UK)