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Recombinant vaccines for poultry: the use of attenuated Eimeria acervulina as a novel live delivery vehicle for viral vaccines

Reference	BB/H020195/2
Principal Investigator / Supervisor	Professor Fiona Tomley
Co-Investigators / Co-Supervisors	Professor Damer Blake
Institution	Royal Veterinary College
Department	Pathology and Pathogen Biology
Funding type	Research
Value (£)	508,311
Status	Completed
Type	Research Grant
Start date	28/06/2011
End date	27/12/2014
Duration	42 months

Abstract

Chickens are the most numerous livestock species in the world. Industrial and political demand for effective, cheap vaccines against infectious diseases that can compromise poultry production, cause severe animal welfare problems and have serious potential for infecting humans has never been higher, particularly set against the pressing needs of global food security. Whilst immunoprotective antigens have been identified for many viral pathogens that infect poultry the commercial development of delivery vectors has been limited to fowlpox virus and a herpes virus of turkeys, both of which require invasive single bird treatment. The ability of Eimeria to induce potent life-long protective immunity after a single self-limiting, host-specific infection and the robust longevity of the oocyst phase of the lifecycle, combined with the recent development of stable transfection strategies for these parasites, promotes their use as novel vectors. Attenuated Eimeria parasites are already extensively used as anticoccidial vaccines. In partnership with Intervet/Schering-Plough Animal Health we propose to investigate the vector potential of Eimeria using Eimeria acervulina as a model to deliver well characterised antigens from two persistently problematic viruses of poultry, infectious bursal disease virus (IBDV) and infectious laryngotracheitis virus (ILTV). Transfection constructs developed for use with Eimeria tenella will be tested with E. acervulina and modified to express the vaccinal antigens IBDV VP2 or ILTV gB, supported by new next-generation derived genomic resources for the recipient. Constructs designed to control the site or timing of transgene expression will be developed and tested to identify the best combination on the basis of ability to induce host immune responses and provide protection against viral challenge. This project is expected to produce parasite lines suitable for use as new vaccines and data supporting the use of Eimeria as vaccine vectors.

Summary

More than 50 billion chickens are produced each year in the world and control of infectious diseases is of primary concern to the poultry industry. Viral, bacterial and parasitic infections compromise the economics and efficiency of meat and egg production, cause severe animal welfare problems and in some cases have serious potential for infecting humans. Demand for effective, cheap vaccines against a broad panel of pathogens has never been higher, particularly set against the pressing needs of global food security. For many viral infections of poultry, we understand which parts of the virus are needed to induce strong protective immunity and could be in a good position to develop new kinds of recombinant 'vectored' vaccines that would be safe, cheap and effective. However the development of organisms that could be used as the vaccine delivery 'vectors' has so far seen commercialisation of only two based on fowlpox virus (FWPV) and herpes virus of turkeys (HVT). Both of these suffer some drawbacks, especially because they have to be given by individual scarification or injection and cannot be administered in a simpler way such as in drinking water or by aerosol spray over large numbers of chicks. Eimeria are host-specific protozoan parasites that transmit between birds by the faecal-oral route and rapidly establish acute intestinal infections that are self-limiting (7-14 days) and induce life-long protective immunity. In poultry they cause coccidiosis, one of the most globally important infections that afflicts the industry, causing severe losses unless controlled by chemotherapy or vaccination. Vaccines using laboratory-derived lines of live-attenuated Eimeria are given in the drinking water and are well established and very effective. The world-leading Eimeria vaccine is Paracox, manufactured by Intervet/Schering-Plough Animal Health, and this sells > 1 billion doses each year and has an exemplary record of safety and efficacy. In our lab we have recently developed methods that allow us to manipulate the genetic material of Eimeria parasites which means we can now make stable transgenic parasite lines; this means it is possible to try and develop Eimeria parasites as vaccine vectors for vaccinal antigens. Recombinant vaccines based on an Eimeria vector would have several advantages over existing vaccines. Because the parasites have large genomes it is likely that we will be able to insert and express vaccine antigens from several different organisms within a single parasite line so a single vaccine could protect against several diseases. These parasites are already licensed as live vaccines and are known to be extremely safe; they infect only chickens and they are completely cleared from the host by 14 days after vaccination. They are known to induce a broad range of potent immune responses so they are likely to be useful for inducing immunity to different kinds of pathogens (viruses, other parasites, bacteria). We propose to investigate the vaccine vector potential of an attenuated Eimeria parasite (E. acervulina HP, one of the Paracox parasites) using well characterised antigens from two important viruses of poultry. The first is infectious bursal disease virus (IBDV), which causes Gumboro, an immunosuppressive disease of poultry that poses severe problems in health and productivity and also interferes with the efficacy of vaccination programmes. IBDV is a particular problem in the broiler industry at the moment with new virulent and variant strains emerging that are able to break through existing vaccines. The second is infectious laryngotracheitis virus, a persistent problem particularly in breeding and commercial layer flocks and for which strong cellular immunity as well as antibody responses are required for effective control.

Committee	Research Committee A (Animal disease, health and welfare)
Research Topics	Animal Health, Immunology, Microbiology, Technology and Methods Development
Research Priority	Animal Health, Global Security
Research Initiative	X - not in an Initiative
Funding Scheme	Industrial Partnership Award (IPA)

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