The role of antigen in the maintenance and localisation of CD8+ T-cells in the context of liver stage malaria
<p>A highly effective vaccine against malaria is urgently needed, with leading vaccination strategies involving the induction of protective antigen-specific CD8<sup>+</sup> T-cells via heterologous prime-boost viral vector immunization, targeting primarily the pre- erythrocytic liv...
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| Format: | Thesis |
| Language: | English |
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2018
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| _version_ | 1817933056344850432 |
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| author | Gola, A |
| author2 | Spencer, A |
| author_facet | Spencer, A Gola, A |
| author_sort | Gola, A |
| collection | OXFORD |
| description | <p>A highly effective vaccine against malaria is urgently needed, with leading vaccination strategies involving the induction of protective antigen-specific CD8<sup>+</sup> T-cells via heterologous prime-boost viral vector immunization, targeting primarily the pre- erythrocytic liver stages of the Plasmodium falciparum lifecycle. To date, the greatest immunogenicity has been obtained through a heterologous prime boost regimen, where vaccination with an Adenoviral vector is followed 8 weeks later by a Modified Vaccinia Ankara virus (MVA) boost. Experimental work directed at providing a greater understanding of CD8<sup>+</sup> T-cell memory responses induced by Ad-MVA vaccinations lead to the development of a novel vaccine strategy aimed at priming CD8<sup>+</sup> T-cells in the periphery and subsequently targeting them to hepatic tissue with protein loaded poly(lactic- co-glycolic acid) nanoparticles or recombinant viral vectors. Durable Ag-specific CD8+ T- cells exhibiting a phenotype of tissue-resident memory T-cells were generated in the liver, with a ten-fold increase over the conventional heterologous vector regimen. Importantly, in P. berghei sporozoite challenge models of liver-stage malaria, this strategy was found to result in unprecedented levels of sterile protection across multiple clinically relevant antigens and mouse strains. This prime and target immunization strategy for liver-stage malaria may provide a novel general approach for prevention or immunotherapy against other hepato-trophic pathogens.</p> |
| first_indexed | 2024-03-06T21:50:34Z |
| format | Thesis |
| id | oxford-uuid:4b1ce436-316f-43da-bacf-3b1e178f2f40 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-12-09T03:47:44Z |
| publishDate | 2018 |
| record_format | dspace |
| spelling | oxford-uuid:4b1ce436-316f-43da-bacf-3b1e178f2f402024-12-08T10:30:09ZThe role of antigen in the maintenance and localisation of CD8+ T-cells in the context of liver stage malariaThesishttp://purl.org/coar/resource_type/c_db06uuid:4b1ce436-316f-43da-bacf-3b1e178f2f40VaccinologyImmunologyLiver-Stage MalariaEnglishORA Deposit2018Gola, ASpencer, AHill, AGermain, R<p>A highly effective vaccine against malaria is urgently needed, with leading vaccination strategies involving the induction of protective antigen-specific CD8<sup>+</sup> T-cells via heterologous prime-boost viral vector immunization, targeting primarily the pre- erythrocytic liver stages of the Plasmodium falciparum lifecycle. To date, the greatest immunogenicity has been obtained through a heterologous prime boost regimen, where vaccination with an Adenoviral vector is followed 8 weeks later by a Modified Vaccinia Ankara virus (MVA) boost. Experimental work directed at providing a greater understanding of CD8<sup>+</sup> T-cell memory responses induced by Ad-MVA vaccinations lead to the development of a novel vaccine strategy aimed at priming CD8<sup>+</sup> T-cells in the periphery and subsequently targeting them to hepatic tissue with protein loaded poly(lactic- co-glycolic acid) nanoparticles or recombinant viral vectors. Durable Ag-specific CD8+ T- cells exhibiting a phenotype of tissue-resident memory T-cells were generated in the liver, with a ten-fold increase over the conventional heterologous vector regimen. Importantly, in P. berghei sporozoite challenge models of liver-stage malaria, this strategy was found to result in unprecedented levels of sterile protection across multiple clinically relevant antigens and mouse strains. This prime and target immunization strategy for liver-stage malaria may provide a novel general approach for prevention or immunotherapy against other hepato-trophic pathogens.</p> |
| spellingShingle | Vaccinology Immunology Liver-Stage Malaria Gola, A The role of antigen in the maintenance and localisation of CD8+ T-cells in the context of liver stage malaria |
| title | The role of antigen in the maintenance and localisation of CD8+ T-cells in the context of liver stage malaria |
| title_full | The role of antigen in the maintenance and localisation of CD8+ T-cells in the context of liver stage malaria |
| title_fullStr | The role of antigen in the maintenance and localisation of CD8+ T-cells in the context of liver stage malaria |
| title_full_unstemmed | The role of antigen in the maintenance and localisation of CD8+ T-cells in the context of liver stage malaria |
| title_short | The role of antigen in the maintenance and localisation of CD8+ T-cells in the context of liver stage malaria |
| title_sort | role of antigen in the maintenance and localisation of cd8 t cells in the context of liver stage malaria |
| topic | Vaccinology Immunology Liver-Stage Malaria |
| work_keys_str_mv | AT golaa theroleofantigeninthemaintenanceandlocalisationofcd8tcellsinthecontextofliverstagemalaria AT golaa roleofantigeninthemaintenanceandlocalisationofcd8tcellsinthecontextofliverstagemalaria |