Vaccine and assay development for nairoviral diseases
Emerging zoonotic diseases present a significant risk to global public health, as evidenced by the ongoing COVID-19 pandemic. Nairoviruses are a genus of viruses, which include Crimean Congo Haemorrhagic Fever Virus (CCHFV) and Nairobi Sheep Disease Virus (NSDV), and present a significant risk of ep...
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| Format: | Thesis |
| Language: | English |
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2022
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| _version_ | 1797109365422948352 |
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| author | Gilbride, C |
| author2 | Lambe, T |
| author_facet | Lambe, T Gilbride, C |
| author_sort | Gilbride, C |
| collection | OXFORD |
| description | Emerging zoonotic diseases present a significant risk to global public health, as evidenced by the ongoing COVID-19 pandemic. Nairoviruses are a genus of viruses, which include Crimean Congo Haemorrhagic Fever Virus (CCHFV) and Nairobi Sheep Disease Virus (NSDV), and present a significant risk of epidemics in humans and animals. As such there is an urgent need to develop effective therapeutics and prophylactics to protect humans and livestock from nairovirus mediated infection and disease. Vaccines are a highly effective healthcare intervention, and ChAdOx vaccine platforms have been used extensively to develop vaccines against emerging diseases, including the ChAdOx1-nCoV19/AZD1222 vaccine. This thesis aims to characterise the development of ChAdOx vectored vaccines against a range of nairoviral antigens, and determine if nairoviral vaccines in ChAdOx vectors are immunogenic following vaccination in mice. As part of this thesis, new pseudotyping assays using CCHFV and NSDV glycoproteins were developed to test neutralising antibody responses induced following vaccination. This thesis demonstrated that CCHFV GPC (GlycoProtein Precursor), Gn, Gc, and NP (Nucleoprotein) antigens were all immunogenic, inducing cellular and humoral responses, and that ChAdOx vectored CCHFV GPC vaccination could induce neutralising antibodies. Further the immunogenicity of NSDV GPC, Gc, and NP antigens in ChAdOx1 vectors was demonstrated following vaccination. Development of multivalent ChAdOx1 CCHFV vaccines showed that a single vaccination could induce broad cellular and humoral immune responses. Anti-vector neutralisation responses induced by vaccination were also assayed in the ChAdOx1-nCoV19 vaccine clinical trial at the University of Oxford. The work in this thesis determined that no correlations were measured between anti-ChAdOx1 neutralisation titres and anti-SARS-CoV-2 spike immune responses following vaccination with ChAdOx1-nCoV19/AZD1222. Overall, this thesis highlights the development of immunogenic vaccines against the emerging pathogens CCHFV and NSDV, which will be crucial to managing future epidemics. |
| first_indexed | 2024-03-07T07:40:52Z |
| format | Thesis |
| id | oxford-uuid:62eb9914-6e76-4c0a-9939-66d07a6ab037 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:40:52Z |
| publishDate | 2022 |
| record_format | dspace |
| spelling | oxford-uuid:62eb9914-6e76-4c0a-9939-66d07a6ab0372023-04-19T09:09:56ZVaccine and assay development for nairoviral diseasesThesishttp://purl.org/coar/resource_type/c_db06uuid:62eb9914-6e76-4c0a-9939-66d07a6ab037Assay developmentVaccine DevelopmentEnglishHyrax Deposit2022Gilbride, CLambe, TGilbert, SBailey, DEmerging zoonotic diseases present a significant risk to global public health, as evidenced by the ongoing COVID-19 pandemic. Nairoviruses are a genus of viruses, which include Crimean Congo Haemorrhagic Fever Virus (CCHFV) and Nairobi Sheep Disease Virus (NSDV), and present a significant risk of epidemics in humans and animals. As such there is an urgent need to develop effective therapeutics and prophylactics to protect humans and livestock from nairovirus mediated infection and disease. Vaccines are a highly effective healthcare intervention, and ChAdOx vaccine platforms have been used extensively to develop vaccines against emerging diseases, including the ChAdOx1-nCoV19/AZD1222 vaccine. This thesis aims to characterise the development of ChAdOx vectored vaccines against a range of nairoviral antigens, and determine if nairoviral vaccines in ChAdOx vectors are immunogenic following vaccination in mice. As part of this thesis, new pseudotyping assays using CCHFV and NSDV glycoproteins were developed to test neutralising antibody responses induced following vaccination. This thesis demonstrated that CCHFV GPC (GlycoProtein Precursor), Gn, Gc, and NP (Nucleoprotein) antigens were all immunogenic, inducing cellular and humoral responses, and that ChAdOx vectored CCHFV GPC vaccination could induce neutralising antibodies. Further the immunogenicity of NSDV GPC, Gc, and NP antigens in ChAdOx1 vectors was demonstrated following vaccination. Development of multivalent ChAdOx1 CCHFV vaccines showed that a single vaccination could induce broad cellular and humoral immune responses. Anti-vector neutralisation responses induced by vaccination were also assayed in the ChAdOx1-nCoV19 vaccine clinical trial at the University of Oxford. The work in this thesis determined that no correlations were measured between anti-ChAdOx1 neutralisation titres and anti-SARS-CoV-2 spike immune responses following vaccination with ChAdOx1-nCoV19/AZD1222. Overall, this thesis highlights the development of immunogenic vaccines against the emerging pathogens CCHFV and NSDV, which will be crucial to managing future epidemics. |
| spellingShingle | Assay development Vaccine Development Gilbride, C Vaccine and assay development for nairoviral diseases |
| title | Vaccine and assay development for nairoviral diseases |
| title_full | Vaccine and assay development for nairoviral diseases |
| title_fullStr | Vaccine and assay development for nairoviral diseases |
| title_full_unstemmed | Vaccine and assay development for nairoviral diseases |
| title_short | Vaccine and assay development for nairoviral diseases |
| title_sort | vaccine and assay development for nairoviral diseases |
| topic | Assay development Vaccine Development |
| work_keys_str_mv | AT gilbridec vaccineandassaydevelopmentfornairoviraldiseases |