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Comparative evaluation of the immunological mechanisms underlying the induction of protection by vaccine candidates based on naturally attenuated isolate and mutants strains of African swine fever virus

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  • Full or part time
    Dr Dixon
    Dr Graham
  • Application Deadline
    Applications accepted all year round

Project Description

African swine fever (ASF) is one of the most devastating diseases for the swine industry against which there is no vaccine available. Recent studies carried out in our group have demonstrated that live attenuated vaccine candidates based on the naturally attenuated African swine fever virus (ASFV) isolate OURT88/3 and deletion mutants strains of virulent viruses can induce protection against lethal challenge with high virulent isolates. Protection can be induced by administration of the attenuated strains by the intramuscular or intranasal routes. Not all pigs are protected and an important goal is to identify the host immune responses that correlate with protection.
However, little is known about the immunological mechanisms underlying the induction of protection Both NK cells and T-cell (CD8+) responses have been suggested to have roles in protection in combination with a potentially protective humoral response. It is known that cytokines are responsible for directing most of the biological effects in the immune system. Like other viruses, ASFV has developed strategies to manipulate the cytokine response to modulate the outcome of the infection. Although some studies have suggested the possible role of interferon (IFNs) in directing protection against ASFV, the role of cytokines in regulating protective immune responses in vivo has been poorly studied to date.

Main objectives:
The main aim of this project will be to improve knowledge of protection mechanisms elicited by live attenuated ASFV vaccine candidates. To achieve this, the following objectives will be followed:
1) Determining (by ELISA and RT-PCR) the differences in cytokine profiles in blood and serum samples between immunised pigs that are protected and non-protected pigs after vaccination with attenuated strains and challenge with virulent ASFV strains. The potential role played by pro-inflammatory and anti-inflammatory cytokines will be investigated.
2) Determining the role of the humoral and cellular immune response in the protection induced by the different vaccine candidates by sero-neutralization tests and assays of cellular responses.
3) Evaluating the role of the mucosal immune system in the protection of pigs by studying the role of tonsils, regional lymph and lung. Virus-cell interactions as well as the local immune response will be investigated using different methods.
4) Evaluating the evolution and role of immunoglobulins (IgM, IgG and IgA) from blood, saliva and mucosal secretions in virus neutralisation.

Funding Notes

Open to self-funded students only; you must have access to your own funding. See full advert for typical annual costs. The studentship is a collaborative project with The University of Surrey; fees 2015/16 £2,025 pa for UK/EU students, £8,400 pa for overseas students (subject to inflation).
Open to biological and veterinary science graduates (with, or who anticipate obtaining, at least a 2.1 or equivalent in their undergraduate degree, or a Masters degree - subject to university regulations).
Students without English as a first language must provide evidence of IELTS score of 7.0 and no less than 6.5 in subsections.

References

Fishbourne, E.; Hutet, E.; Abrams, C.; Cariolet, R.; Potier, M. F. le; Takamatsu, H. H.; Dixon, L. K. 2013 Increase in chemokines CXCL10 and CCL2 in blood from pigs infected with high compared to low virulence African swine fever virus isolates. Veterinary Research, 44, Article Number 87 ISSN:1297-9716
King, K , Chapman, D Argilaguet, JM ; Fishbourne, E., Hutet, E Cariolet, R Hutchings, G, Oura, CAL, Netherton, CL , Moffat, K , Taylor, G , Le Potier, MF , Dixon, LK , Takamatsu, HH 2011 Protection of European domestic pigs from virulent African isolates of African swine fever virus. Vaccine, 2011. 29: 4593-4600
Chapman, DAG., Tcherepanov, V., Upton C. and Dixon LK. 2008 Comparison of the genome sequences of non-pathogenic and pathogenic African swine fever virus isolates J Gen Virol ; 89: 397-408.
Oura, C.A.L., et al., Journal of General Virology, 2005. 86: p. 2445-2450.
Onisk, D.V., et al., Virology, 1994. 198: 350-354.

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