Glycoengineering of Veterinary Vaccines

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A healthily maintained livestock is essential for the economy and prosperity of the UK. Additionally some infected livestock are the source of human diseases, particularly through foodborne infections. Historically, vaccines have been the most successful and effective intervention to reduce the burden of infectious diseases in humans. By contrast, the application of vaccines in veterinary medicine is rudimentary, mainly due to the economic necessity for reduced costs to vaccinate animals and because our knowledge of the pathogens that cause animal diseases lags behind that of human counterparts. A defining characteristic of a successful vaccine is the ability to evoke long-lasting protective immunity with minimal side effects. Many of the most successful human vaccines are glycoconjugates, a combination of a protein coupled to a glycan, which induces both a T-cell dependent and independent immune response generating a protective and lasting immunity. Examples of currently licensed human glycoconjugate vaccines include those against Haemophilus influenzae, Neisseria meningitidis and Streptococcus pneumoniae, in which glycans (lipopolysaccharides or capsular polysaccharides) are chemically coupled to immunogenic carrier proteins. However, the production of these vaccines requires multistep procedures that are often complex and expensive, and can exhibit batch-to-batch variation.We recently developed Protein Glycan Coupling Technology (PGCT) that can overcome the complex procedures required for chemically synthesising glycoconjugate vaccines by expressing the vaccine in an Escherichia coli cell in a single-step procedure. The advantages of applying PGCT to veterinary vaccines are (i) glycoconjugate vaccines can be produced at low cost, (ii) the flexibility of coupling "any glycan" with "any protein" facilitates the production of vaccine combinations providing the opportunity to evaluate a greater variety of vaccine candidates, and (iii) combination vaccines against more than one disease can be produced, further reducing cost and obviating the need to administer multiple vaccines (or antibiotics).In this study we will use PGCT to produce inexpensive triple combination poultry vaccines to reduce infection from E. coli, Salmonella, Campylobacter jejuni/coli and C. perfringens. This will not only protect poultry flocks from severe disease but would also protect the human population from the most common foodborne infections including those caused by Salmonella and Campylobacter. In addition we will construct and evaluate a dual Coxiella/C. perfringens vaccine to protect cattle, sheep and goats against severe disease. This vaccine would also prevent the spread of Q-fever to humans, which is caused by the highly infectious Coxiella burnetii pathogen. The principles developed in this proposal could subsequently be widely applied to produce inexpensive efficacious vaccines against most animal species and promise to break new ground in veterinary vaccine production.