Evaluation of African swine fever vaccine candidates by transcription profiling and assessment of immune responses

Lead Research Organisation: University of Oxford
Department Name: Interdisciplinary Bioscience DTP

Abstract

African swine fever (ASE) is one of the most devastating diseases for the swine industry. This project
will advance the development of an effective vaccine. This would be of immense value to control the
disease in Africa as well as prevent further spread of ASF in Russia and E. Europe. We have deleted
several genes involved in suppressing induction of type I interferon (IFN) transcription from virulent
ASF virus (ASFV) isolates. Type I lENs are known to be crucial in the control and induction of
protective immune mechanisms following virus infection. Inoculation of pigs with these deletion
mutants has demonstrated virus attenuation as well as pig protection (80-100%) against challenge
with lethal doses of parental virulent isolates of ASFV. Thus, deletion of these genes is a promising
route for construction of rationally attenuated ASEV candidate vaccine strains. However, not all pigs
have been protected and an important goal is to identify the host immune responses that correlate
with protection.
The aim of this project will be to investigate the host responses to different ASFV deletion mutant
vaccine candidates to identify those which correlate with effective protection. To achieve this, the
project will investigate differences in global transcription profiles, the expression of selected
immunomodulators and induction of cellular and humoral immune responses in protected
compared to unprotected pigs.
The project will provide training in virology, (including working at high containment SAPO4 level,
virus growth and titration), gene expression analysis (by RNA sequencing and qRTPCR), immunology
(using advanced multi-colour flow cytometry analysis to phenotype porcine immmunocompetent
subsets, the use of intra-cytoplasmic staining to detect cytokine expression, the use of magnetic
based cell sorting, analysis of antibody responses). Through involvement and a placement at Zoetis,
a world leader in veterinary vaccine development, the student will be trained in methods for scaling
up cell culture of vaccine strains in a commercial environment. The student will also have the
opportunity to gain experience in other areas of the company which may include preparation of the
documentation for vaccine registration or sales and marketing steps. Involvement of the Jenner
Institute will provide access to state of the art expertise in vaccine evaluation including the core
transcriptomics unit. The training will enable development of broad competences in immunology,
virology and molecular biology with special attention to the cells and pathways that initiate immune
responses following infection or vaccination.
The student will be based at The Pirbright Institute in Surrey in the African swine fever virus group.
The 12 week placement will be carried out at the Zoetis site, Olot, Girona, Spain. Regular meetings
will be held with the Oxford University supervisor based in the Jenner Institute, Oxford.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M011224/1 01/10/2015 30/09/2023
1801371 Studentship BB/M011224/1 01/10/2016 30/09/2020 Samuel Connell
 
Description Investigation of Viral genes that evade innate immunity 
Organisation University of Illinois
Country United States 
Sector Academic/University 
PI Contribution Exchange visit and reagents, and discussion with collaborators from University of Illinois
Collaborator Contribution Exchange visit and reagents, and discussion with collaborators from University of Illinois
Impact No current outcomes.
Start Year 2017
 
Description Investigation of Viral genes that evade innate immunity 
Organisation University of London
Country United Kingdom 
Sector Academic/University 
PI Contribution Exchange visit and reagents, and discussion with collaborators from St George's University of London
Collaborator Contribution Exchange visit and reagents, and discussion with collaborators from St George's University of London
Impact No outcomes yet.
Start Year 2017