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EASTBIO The chicken or the egg; unravelling immunological mechanisms of in ovo vaccination


Project Description

Royal (Dick) School of Veterinary Studies / The Roslin Institute

In ovo vaccination is an alternative approach to post-hatch vaccination of chickens. It is a safe, animal and user-friendly method that enables vaccination ~60,000 eggs per hour. The technology has been well developed for vaccination against Marek’s Disease virus and efforts to extend the technology for other viral vaccines including Newcastle Disease Virus, Infectious Bursal Disease Virus (IBDV), and bacterial and parasitic vaccines are in progress. Although in ovo vaccination is highly successful, the immunological mechanisms behind its efficacy are unknown. The vaccines are deposited into the extra-embryonic compartment, mainly into the amniotic sac. The embryo ingests the surrounding amnion fluid with the vaccine which are taken up by immune cells of the gut associated lymphoid system. There are some indications that other sites are involved in uptake of the antigens and induction of immune responses, including the respiratory tract through the presence of a choanal cleft that communicates with the nasal and oral cavities, and cloaca through cloacal drinking. The in ovo vaccines that are currently used in the poultry industry are live replicating viruses. To extend and improve this technology for application of inactivated vaccines or adjuvanted subunit vaccines, it is important to better understand the processes that occur after in ovo application. This project addresses the following questions: (i) where does antigen localise after in ovo application, (ii) where are the immune responses induced, and (iii) what type of immune responses are induced in the embryo and post hatch, with the ultimate goal to enhance uptake of vaccines and improve protective immune responses.

Three types of antigen will be used to provide a wide range of immune responses, innate and adaptive both humoral and cellular responses; a model antigen cholera toxin B-subunit (CT-B), a detoxified protein known to bind to epithelial cells and to induce strong immune responses, a live replicating IBDV vaccine strain expected to induce humoral and cellular responses, and a non-replicating inactivated IBDV strain, expected to induce humoral responses. Addition of compounds to stimulate the immune system may be tested to boost the responses.

More recently, unique tools to visualise the immune system of the chicken have been developed at The Roslin Institute. In this project, CSF1R-transgenic reporter chickens will be used in which cells of the mononuclear phagocyte system express a fluorescent protein.1,2
Combined with state of the art bio-imaging (https://www.ed.ac.uk/roslin/facilities-resources/bioimaging), the location and uptake of fluorescent antigen or virus (CT-B and IBDV) can be traced. The immune responses will be investigated at cellular level using flow cytometry, bio-imaging, ELIspot assay and Elisa and at mRNA level using RT-qPCR and large scale RT-qPCRs using Fluidigm arrays.
The outcomes of this proposal are multifaceted and the student will be trained in state of the art techniques, generate basic scientific knowledge as well as knowledge that is translated into vaccine development. This studentship is a collaborative project with MSD Animal Health and the placement will enable MSD-AH to teach students the essential technical and business skills needed to meet current and future industrial needs.

Eligibility:
All candidates should have or expect to have a minimum of an appropriate upper 2nd class degree. To qualify for full funding students must be UK or EU citizens who have been resident in the UK for 3 years prior to commencement.

Funding Notes

Applications:
Completed application form along with your supporting documents should be sent to our PGR student team at

References:
Please send the reference request form to two referees. Completed forms for University of Edinburgh, Royal (Dick) School of Veterinary Studies and the Roslin Institute project should be returned to by the closing date: 5th January 2020.

It is your responsibility to ensure that references are provided by the specified deadline.
Download application and reference forms via:
View Website

References

1. Front. Immunol., 2019 doi.org/10.3389/fimmu.2019.02495
2. Vet Res., 2018 doi:10.1186/s13567-018-0598-7

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