A phase I trial evaluating the safety and immunogenicity of a candidate tuberculosis vaccination regimen, ChAdOx1 85A prime - MVA85A boost in healthy UK adults
<p><strong>BACKGROUND:</strong> This phase I trial evaluated the safety and immunogenicity of a candidate tuberculosis vaccination regimen, ChAdOx1 85A prime-MVA85A boost, previously demonstrated to be protective in animal studies, in healthy UK adults.</p> <p><stron...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Elsevier
2019
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| _version_ | 1797069914917306368 |
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| author | Wilkie, M Satti, I Minhinnick, A Harris, S Riste, M Ramon, R Sheehan, S Thomas, Z Wright, D Stockdale, L Hamidi, A O'Shea, M Dwivedi, K Behrens, H Davenne, T Morton, J Vermaak, S Lawrie, A Moss, P McShane, H |
| author_facet | Wilkie, M Satti, I Minhinnick, A Harris, S Riste, M Ramon, R Sheehan, S Thomas, Z Wright, D Stockdale, L Hamidi, A O'Shea, M Dwivedi, K Behrens, H Davenne, T Morton, J Vermaak, S Lawrie, A Moss, P McShane, H |
| author_sort | Wilkie, M |
| collection | OXFORD |
| description | <p><strong>BACKGROUND:</strong> This phase I trial evaluated the safety and immunogenicity of a candidate tuberculosis vaccination regimen, ChAdOx1 85A prime-MVA85A boost, previously demonstrated to be protective in animal studies, in healthy UK adults.</p> <p><strong>METHODS:</strong> We enrolled 42 healthy, BCG-vaccinated adults into 4 groups: low dose Starter Group (n = 6; ChAdOx1 85A alone), high dose groups; Group A (n = 12; ChAdOx1 85A), Group B (n = 12; ChAdOx1 85A prime - MVA85A boost) or Group C (n = 12; ChAdOx1 85A - ChAdOx1 85A prime - MVA85A boost). Safety was determined by collection of solicited and unsolicited vaccine-related adverse events (AEs). Immunogenicity was measured by antigen-specific ex-vivo IFN-γ ELISpot, IgG serum ELISA, and antigen-specific intracellular IFN-γ, TNF-α, IL-2 and IL-17.</p> <p><strong>RESULTS:</strong> AEs were mostly mild/moderate, with no Serious Adverse Events. ChAdOx1 85A induced Ag85A-specific ELISpot and intracellular cytokine CD4+ and CD8+ T cell responses, which were not boosted by a second dose, but were boosted with MVA85A. Polyfunctional CD4+ T cells (IFN-γ, TNF-α and IL-2) and IFN-γ+, TNF-α+ CD8+ T cells were induced by ChAdOx1 85A and boosted by MVA85A. ChAdOx1 85A induced serum Ag85A IgG responses which were boosted by MVA85A.</p> <p><strong>CONCLUSION:</strong> A ChAdOx1 85A prime - MVA85A boost is well tolerated and immunogenic in healthy UK adults.</p> |
| first_indexed | 2024-03-06T22:31:26Z |
| format | Journal article |
| id | oxford-uuid:5869a47f-58c4-4222-b1e2-beefd7e168f6 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:31:26Z |
| publishDate | 2019 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:5869a47f-58c4-4222-b1e2-beefd7e168f62022-03-26T17:03:17ZA phase I trial evaluating the safety and immunogenicity of a candidate tuberculosis vaccination regimen, ChAdOx1 85A prime - MVA85A boost in healthy UK adultsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:5869a47f-58c4-4222-b1e2-beefd7e168f6EnglishSymplectic Elements at OxfordElsevier2019Wilkie, MSatti, IMinhinnick, AHarris, SRiste, MRamon, RSheehan, SThomas, ZWright, DStockdale, LHamidi, AO'Shea, MDwivedi, KBehrens, HDavenne, TMorton, JVermaak, SLawrie, AMoss, PMcShane, H<p><strong>BACKGROUND:</strong> This phase I trial evaluated the safety and immunogenicity of a candidate tuberculosis vaccination regimen, ChAdOx1 85A prime-MVA85A boost, previously demonstrated to be protective in animal studies, in healthy UK adults.</p> <p><strong>METHODS:</strong> We enrolled 42 healthy, BCG-vaccinated adults into 4 groups: low dose Starter Group (n = 6; ChAdOx1 85A alone), high dose groups; Group A (n = 12; ChAdOx1 85A), Group B (n = 12; ChAdOx1 85A prime - MVA85A boost) or Group C (n = 12; ChAdOx1 85A - ChAdOx1 85A prime - MVA85A boost). Safety was determined by collection of solicited and unsolicited vaccine-related adverse events (AEs). Immunogenicity was measured by antigen-specific ex-vivo IFN-γ ELISpot, IgG serum ELISA, and antigen-specific intracellular IFN-γ, TNF-α, IL-2 and IL-17.</p> <p><strong>RESULTS:</strong> AEs were mostly mild/moderate, with no Serious Adverse Events. ChAdOx1 85A induced Ag85A-specific ELISpot and intracellular cytokine CD4+ and CD8+ T cell responses, which were not boosted by a second dose, but were boosted with MVA85A. Polyfunctional CD4+ T cells (IFN-γ, TNF-α and IL-2) and IFN-γ+, TNF-α+ CD8+ T cells were induced by ChAdOx1 85A and boosted by MVA85A. ChAdOx1 85A induced serum Ag85A IgG responses which were boosted by MVA85A.</p> <p><strong>CONCLUSION:</strong> A ChAdOx1 85A prime - MVA85A boost is well tolerated and immunogenic in healthy UK adults.</p> |
| spellingShingle | Wilkie, M Satti, I Minhinnick, A Harris, S Riste, M Ramon, R Sheehan, S Thomas, Z Wright, D Stockdale, L Hamidi, A O'Shea, M Dwivedi, K Behrens, H Davenne, T Morton, J Vermaak, S Lawrie, A Moss, P McShane, H A phase I trial evaluating the safety and immunogenicity of a candidate tuberculosis vaccination regimen, ChAdOx1 85A prime - MVA85A boost in healthy UK adults |
| title | A phase I trial evaluating the safety and immunogenicity of a candidate tuberculosis vaccination regimen, ChAdOx1 85A prime - MVA85A boost in healthy UK adults |
| title_full | A phase I trial evaluating the safety and immunogenicity of a candidate tuberculosis vaccination regimen, ChAdOx1 85A prime - MVA85A boost in healthy UK adults |
| title_fullStr | A phase I trial evaluating the safety and immunogenicity of a candidate tuberculosis vaccination regimen, ChAdOx1 85A prime - MVA85A boost in healthy UK adults |
| title_full_unstemmed | A phase I trial evaluating the safety and immunogenicity of a candidate tuberculosis vaccination regimen, ChAdOx1 85A prime - MVA85A boost in healthy UK adults |
| title_short | A phase I trial evaluating the safety and immunogenicity of a candidate tuberculosis vaccination regimen, ChAdOx1 85A prime - MVA85A boost in healthy UK adults |
| title_sort | phase i trial evaluating the safety and immunogenicity of a candidate tuberculosis vaccination regimen chadox1 85a prime mva85a boost in healthy uk adults |
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