Optimising response to oral yeast-based vaccines against coccidiosis in chickens
Lead Research Organisation:
Royal Veterinary College
Department Name: Pathobiology and Population Sciences
Abstract
Humankind is farming more poultry than ever before, with an increasing reliance on poultry meat and eggs for provision of dietary protein for human consumption. Concurrently, we are attempting to reduce routine reliance on drugs to control pathogens, replacing them with vaccines or other strategies. For species such as chickens, these vaccines have to be cheap, reliable, easy to administer and (ideally) use existing distribution pathways in such a way that they are accessible to industry as well as backyard farmers in low- and medium-income countries. Such vaccines should be thermostable and not rely on a constant cool-chain. Unfortunately, scalable and cost-effective vaccines are not available for many pathogens such as Eimeria, cause of the disease coccidiosis in chickens. We and others have recently estimated that coccidiosis costs the UK poultry industry ~£100 million every year, exceeding £10 billion globally. Approximately 40% of the drugs used in British livestock production are required to control these parasites. Live vaccines are available, but represent a four-fold higher cost to the producer and cannot be produced at sufficient scale to replace drugs. A robust, cost-effective alternative is required.
Yeast species such as Saccharomyces cerevisiae are useful tools for the high yield production of recombinant proteins and have a Generally Regarded As Safe (GRAS) status (e.g. United States Food and Drug Agency). They are capable of performing several complex protein modifications that are not achieved in many other expression systems, and are easily grown to very high densities producing large quantities of stable particles. The idea of using S. cerevisiae as a delivery vehicle for cancer, viral, and bacterial vaccines has been explored, inducing robust humoral and cellular immune responses. Recently, we have developed a yeast-delivery platform in which antigens from Eimeria can be expressed in a stable, non-secreted form, with the yeast itself acting as transport system and adjuvant. We have tested this yeast to vaccinate against one form of coccidiosis, inducing control of parasite replication following low-level challenge of chickens at levels better than achieved using other vaccine delivery systems. Here, we propose to develop the yeast delivery system to improve protection against high-level challenge and expand its range to protect against two additional forms of coccidiosis. Combined, these three forms of disease cause the overwhelming majority of the burden of coccidiosis in Europe, North and South America, Asia and Africa. The efficacy of these new vaccines will be tested under commercial conditions, assessing value in terms of farm-level performance and chicken welfare (freedom from disease).
Importantly, heat inactivation of the yeast cells prior to vaccination means that the vaccine is not categorised as a genetically modified organism (GMO) at the time of distribution or administration, and would therefore not be subject to GMO regulations. Additional use of freeze-drying to preserve the heat-killed yeast removes the requirement for a cold chain, reducing transport and storage costs. We will characterise immune responses induced following vaccination and parasite challenge to assess the likely utility of the killed-yeast approach to vaccinate against other important pathogens of poultry. Vaccines based upon S. cerevisiae are likely to be particularly valuable against diseases of farmed poultry, where safety, scalability, stability, delivery and cost are crucial.
Yeast species such as Saccharomyces cerevisiae are useful tools for the high yield production of recombinant proteins and have a Generally Regarded As Safe (GRAS) status (e.g. United States Food and Drug Agency). They are capable of performing several complex protein modifications that are not achieved in many other expression systems, and are easily grown to very high densities producing large quantities of stable particles. The idea of using S. cerevisiae as a delivery vehicle for cancer, viral, and bacterial vaccines has been explored, inducing robust humoral and cellular immune responses. Recently, we have developed a yeast-delivery platform in which antigens from Eimeria can be expressed in a stable, non-secreted form, with the yeast itself acting as transport system and adjuvant. We have tested this yeast to vaccinate against one form of coccidiosis, inducing control of parasite replication following low-level challenge of chickens at levels better than achieved using other vaccine delivery systems. Here, we propose to develop the yeast delivery system to improve protection against high-level challenge and expand its range to protect against two additional forms of coccidiosis. Combined, these three forms of disease cause the overwhelming majority of the burden of coccidiosis in Europe, North and South America, Asia and Africa. The efficacy of these new vaccines will be tested under commercial conditions, assessing value in terms of farm-level performance and chicken welfare (freedom from disease).
Importantly, heat inactivation of the yeast cells prior to vaccination means that the vaccine is not categorised as a genetically modified organism (GMO) at the time of distribution or administration, and would therefore not be subject to GMO regulations. Additional use of freeze-drying to preserve the heat-killed yeast removes the requirement for a cold chain, reducing transport and storage costs. We will characterise immune responses induced following vaccination and parasite challenge to assess the likely utility of the killed-yeast approach to vaccinate against other important pathogens of poultry. Vaccines based upon S. cerevisiae are likely to be particularly valuable against diseases of farmed poultry, where safety, scalability, stability, delivery and cost are crucial.
Technical Summary
In the work proposed here, we intend to improve our application of Saccharomyces cerevisiae as an oral vaccine vector platform for use with poultry, testing alternative intra-cellular compartments for antigen expression and the value of immune targeting epitopes. We will build on our recent studies demonstrating that heat-killed, freeze dried yeast can be used for oral delivery of anticoccidial vaccine candidates to chickens, inducing immune responses that limit Eimeria tenella replication following low-dose challenge at a level equivalent to modern ionophore chemoprophylaxis. Each new yeast-vectored vaccine will be tested for protective capacity against high-level E. tenella challenge, assessing traits that are relevant to production and welfare including body weight gain (BWG) and lesion score (LS). The optimised yeast vector will subsequently be used to express validated vaccine antigen homologues for E. acervulina and E. maxima, addressing the three most economically important Eimeria species that infect chickens. The resulting multi-valent vaccine formulation will be tested under field-type conditions, measuring parasite replication, BWG, LS and feed conversion ratio (FCR). Local immune cell phenotypes induced by vaccination with existing and new yeast-vectored vaccines will be defined, assessing their potential as correlates of protection for vaccine development against E. tenella and other enteric pathogens.
Major outputs will include understanding of the breadth of immune responses, systemic and local, stimulated by an oral yeast-vectored vaccine with different yeast cell expression profiles, the influence of immune targeting epitopes, and their interaction with the well-established anticoccidial vaccine candidates apical membrane antigen 1 (AMA1) and immune mapped protein 1 (IMP1). Consideration of immune responses in different chicken body compartments will be used to indicate the range of pathogens that may be rationally targeted in future applications.
Major outputs will include understanding of the breadth of immune responses, systemic and local, stimulated by an oral yeast-vectored vaccine with different yeast cell expression profiles, the influence of immune targeting epitopes, and their interaction with the well-established anticoccidial vaccine candidates apical membrane antigen 1 (AMA1) and immune mapped protein 1 (IMP1). Consideration of immune responses in different chicken body compartments will be used to indicate the range of pathogens that may be rationally targeted in future applications.
Publications
Jaramillo-Ortiz JM
(2023)
First detection and characterisation of Eimeria zaria in European chickens.
in Veterinary parasitology
Description | We have expanded the concept of killed yeast as a safe non-GMO vector for vaccines against parasites that affect chickens. This has included testing against different species of parasites that can cause coccidiosis and assessment of the impact of protein expression location on/within the yeast cell. |
Exploitation Route | These findings are being used as pilot data to interact with industry with the longer term goal of developing new, cheaper and scalable vaccines for coccidiosis in chickens. The platform can also be used to deliver vaccine antigens that target other pathogens of poultry. |
Sectors | Agriculture Food and Drink |
Description | Big data analyses in studies with microbiomes and vaccination outcomes |
Geographic Reach | Europe |
Policy Influence Type | Participation in a guidance/advisory committee |
Description | Coccidiosis and gut health working group |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Participation in a guidance/advisory committee |
Description | Phibro seminar 1 |
Geographic Reach | Asia |
Policy Influence Type | Influenced training of practitioners or researchers |
Impact | Improved use of drugs in livestock production (antimicrobial and antiparasitic) |
Description | Phibro seminar 2 |
Geographic Reach | Asia |
Policy Influence Type | Influenced training of practitioners or researchers |
Impact | Improved use of drugs in livestock production (antimicrobial and antiparasitic) |
Description | Poultry Diseases Group 2022 |
Geographic Reach | National |
Policy Influence Type | Participation in a guidance/advisory committee |
Description | Identification of virulence factors in pathogenic ruminant Eimeria species to inform future vaccination targets and strategies |
Amount | £49,603 (GBP) |
Funding ID | P2108376 |
Organisation | Agricultural and Horticulture Development Board |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 11/2021 |
End | 03/2022 |
Description | The association of GPR35 with chicken intestinal dysbiosis |
Amount | £1,510 (GBP) |
Funding ID | HT/VSG/23/01 |
Organisation | The Houghton Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 06/2023 |
End | 08/2023 |
Description | Yeast-based vaccine platform as a tool to target avian M-cells: an approach for tackling infectious intestinal diseases Yeast-based vaccine platform as a tool to target avian M-cells: an approach for tackling infectious intestinal diseases in chickens |
Amount | £10,162 (GBP) |
Funding ID | HT/SPRG/23/05 |
Organisation | The Houghton Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 08/2023 |
End | 08/2024 |
Description | University of Thessaloniki - impact of Eimeria on chicken performance and alternatives for control |
Organisation | Aristotle University of Thessaloniki |
Country | Greece |
Sector | Academic/University |
PI Contribution | Provision of Eimeria species parasites and expert knowledge related to doses and measures of parasitaemia. |
Collaborator Contribution | In vivo studies exploring the impact of a range of novel controls |
Impact | DOI: 10.3389/fvets.2020.00420. DOI: 10.3390/life12111783. |
Start Year | 2020 |
Description | 13th International Coccidiosis Conference: Jose Jaramillo-Ortiz |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Industry/Business |
Results and Impact | Yeast-vectored oral immunisation in commercial broilers and layer chickens against Eimeria tenella. Ceské Budejovice, Czech Republic. |
Year(s) Of Engagement Activity | 2023 |
Description | Avian Pathology Lecture Award at the XXIInd World Veterinary Poultry Association Congress |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Award presentation to an audience of ~800, primarily veterinarians as well as animal health and breeding company representatives. Discussions and proposals for collaboration followed, plus new links with industry. |
Year(s) Of Engagement Activity | 2023 |
URL | https://www.houghtontrust.org.uk/sponsored-lectures |
Description | DISCONTOOLS Coccidiosis (Poultry) |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Working group and report published updating understanding of the impact and control of coccidiosis |
Year(s) Of Engagement Activity | 2023 |
URL | https://www.discontools.eu/database/68-coccidiosis.html |
Description | Early Career Researcher Event held by the International Veterinary Vaccinology Network (IVVN) |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Contributed to International Veterinary Vaccinology Network (IVVN). |
Year(s) Of Engagement Activity | 2023 |
Description | Industry advisory board meeting on coccidiosis |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Industry/Business |
Results and Impact | Two day advisory board meeting with industry representatives focused on control of coccidiosis in chickens and approaches to fast track new vaccines. Included a panel of international (European + USA) representatives. |
Year(s) Of Engagement Activity | 2022 |
Description | Industry working group exploring use of big data in chicken health |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Industry/Business |
Results and Impact | Industry working group exploring use of big data in chicken health - focus on gut health including microbiota, Eimeria, and the impact of current and novel vaccines. Resulted in a collaboration agreement with new meetings pending. |
Year(s) Of Engagement Activity | 2022 |
Description | International Veterinary Immunology Symposium. Early Career Researchers workshop panel: Jose Jaramillo-Ortiz |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Oral presentation and panel discussion at the International Veterinary Immunology Symposium. Early Career Researchers workshop panel held by members of the IVVN. November 17 - 21. Kruger National Park, South Africa. |
Year(s) Of Engagement Activity | 2023 |
Description | Invited presentation at the Veterinary Research Group |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | Invited presentation to Veterinary Research Club. Online delivery to ~25 people. |
Year(s) Of Engagement Activity | 2023 |
Description | Keynote presentation at the 4th Eimeriana Avia |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Invited keynote presentation to open the 4th Eimeriana Avia. An audience of ~400, primarily veterinarians as well as animal health and breeding company representatives. Discussions and proposals for collaboration followed. |
Year(s) Of Engagement Activity | 2024 |
Description | Poultry Diseases Group meeting - 2022 |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | Discussed project progress and relevance to UK poultry producers at the Poultry Disease Group meeting, a workshop linking veterinary practitioners, industry representatives and academics. |
Year(s) Of Engagement Activity | 2022 |
Description | Presentation 'impact of novel vaccine son microbiomes' - 6th International Meeting on Apicomplexan Parasites in Farm Animals |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | Oral presentation by Dr Po-Yu Liu "Multi-omics analysis reveals regime shifts in the gastrointestinal ecosystem in chickens following anticoccidial vaccination and Eimeria tenella challenge" delivered to the 6th International Meeting on Apicomplexan Parasites in Farm Animals (October 2022) followed by questions from ~120 audience members |
Year(s) Of Engagement Activity | 2022 |
Description | Presentation and training - British Society for Immunology |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Other audiences |
Results and Impact | FACS training and oral presentation: Dr Jose Jaramillo-Ortiz |
Year(s) Of Engagement Activity | 2022 |
Description | Presentation at industry conference (Huvepharma) |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Invited presentation to industry professionals at Huvepharma workshop in Bulgaria. An audience of ~250, primarily veterinarians as well as animal health and breeding company representatives. Discussions and proposals for collaboration followed. |
Year(s) Of Engagement Activity | 2023 |
Description | Presentation at the British Association of Veterinary Parasitology, Early Career Researchers' Meeting |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Postgraduate students |
Results and Impact | Early career researcher meeting of the British Association of Veterinary Parasitology. Oral presentation of project work by Oluwayomi O. Adeyemi. |
Year(s) Of Engagement Activity | 2022 |
Description | Presentation at the British Society of Parasitology, Annual Spring Meeting |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | British Association of Parasitology. Poster presentation of project work by Oluwayomi O. Adeyemi. |
Year(s) Of Engagement Activity | 2022 |
Description | Presentation vaccine development - 6th International Meeting on Apicomplexan Parasites in Farm Animals |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | Oral presentation by Dr Jose Jaramillo-Ortiz "Yeast-vectored oral immunisation in commercial layer chickens against Eimeria tenella" delivered to the 6th International Meeting on Apicomplexan Parasites in Farm Animals (October 2022) followed by questions from ~120 audience members. |
Year(s) Of Engagement Activity | 2022 |
Description | Study workshop at the Norwegian Veterinary Institute |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Postgraduate students |
Results and Impact | Invited presentation to the Norwegian Veterinary Institute and working group participation to explore improved control of Eimeria. |
Year(s) Of Engagement Activity | 2023 |