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Title: The immune response to live, attenuated peste des petits ruminants virus vaccines
Author: Hodgson, Sophia
ISNI:       0000 0004 7960 9344
Awarding Body: University of Surrey
Current Institution: University of Surrey
Date of Award: 2019
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Peste des petits ruminants (PPR) is an economically important disease of sheep and goats caused by infection with the morbillivirus, peste des petits rumiants virus (PPRV). The disease is characterised by high morbidity and mortality and is a World Organisation for Animal Health (OIE) reportable disease. The OIE and Food and Agriculture Organisation (FAO) have agreed to globally eradicate PPR by 2030. Eradication of the disease will lead to improvements in food security and livelihood stability for millions of subsistence and nomadic farmers in some of the world's poorest countries. Vaccination will play a key role in global eradication. Live, attenuated vaccines are available for PPRV and have a long safety and efficacy record, however, the mechanisms of protection are not known. There are four genetic lineages of PPRV, but only one serotype, to improve end-user confidence in the vaccines, vaccination/challenge experiments were performed with the two most widely used live, attenuated vaccines and challenging with representative PPRV strains from all genetic lineages. Both vaccines provided protection against all four genetic lineages. The mechanisms of vaccine-induced protection have not been investigated in detail for these vaccines, so serum and peripheral blood mononuclear cells (PBMCs) collected during the vaccination/challenge experiments were used to study the cellular and serological responses to vaccination. Both vaccines induce PPRV-neutralising antibodies and PPRV-specific proliferative responses and interferon-γ (IFN-γ) production. To investigate the role of CD8+ T cells in vaccine-induced protection goats were vaccinated, injected with the anti-CD8 mAb CC63 and challenged whilst their CD8+ cells were almost undetectable in peripheral blood. CD8-depleted goats did not develop signs of PPRV, but on post mortem some were found to have gut-specific pathology. Therefore, CD8+ T cells are not the primary source of vaccine-induced protection, but they may play a role in tissue-specific protection.
Supervisor: Baron, Michael D. ; Darpel, Karin Sponsor: Bill and Melinda Gates Foundation
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral