Progress in DNA-based heterologous prime-boost immunization strategies for malaria.
An effective vaccine against malaria is urgently required to relieve the immense human suffering and mortality caused by this parasite. A successful subunit vaccine against the liver stage of malaria will require the induction of high levels of protective T cells. Despite success in small animal mod...
| Main Authors: | , |
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| Format: | Journal article |
| Language: | English |
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2004
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| _version_ | 1826269635319693312 |
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| author | Moore, A Hill, A |
| author_facet | Moore, A Hill, A |
| author_sort | Moore, A |
| collection | OXFORD |
| description | An effective vaccine against malaria is urgently required to relieve the immense human suffering and mortality caused by this parasite. A successful subunit vaccine against the liver stage of malaria will require the induction of high levels of protective T cells. Despite success in small animal models, DNA vaccines fail to induce strong cellular immune responses in humans. However, DNA vaccines can induce a T-cell response that can be strongly boosted by recombinant viral vectors. We have evaluated this heterologous prime-boost approach using the Plasmodium berghei mouse model for immunogenicity and protective efficacy against malaria challenge using combinations of plasmid DNA, recombinant modified vaccinia virus Ankara, fowlpox virus, and non-replicating adenovirus. We have proceeded to test immunogenicity and efficacy of successful heterologous prime-boost vaccines in phase I/IIa trials in malaria naïve subjects in the UK and in semi-immune individuals in The Gambia. In these clinical trials, remarkably high levels of effector T-cell responses have been induced and significant protection documented in a human sporozoite challenge model. We summarize the preclinical design and development of these heterologous prime-boost vaccines and discuss the encouraging results that have been observed in vaccinated humans. |
| first_indexed | 2024-03-06T21:28:07Z |
| format | Journal article |
| id | oxford-uuid:43c90b26-6b02-41a4-9825-d4088ffb0069 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:28:07Z |
| publishDate | 2004 |
| record_format | dspace |
| spelling | oxford-uuid:43c90b26-6b02-41a4-9825-d4088ffb00692022-03-26T14:57:34ZProgress in DNA-based heterologous prime-boost immunization strategies for malaria.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:43c90b26-6b02-41a4-9825-d4088ffb0069EnglishSymplectic Elements at Oxford2004Moore, AHill, AAn effective vaccine against malaria is urgently required to relieve the immense human suffering and mortality caused by this parasite. A successful subunit vaccine against the liver stage of malaria will require the induction of high levels of protective T cells. Despite success in small animal models, DNA vaccines fail to induce strong cellular immune responses in humans. However, DNA vaccines can induce a T-cell response that can be strongly boosted by recombinant viral vectors. We have evaluated this heterologous prime-boost approach using the Plasmodium berghei mouse model for immunogenicity and protective efficacy against malaria challenge using combinations of plasmid DNA, recombinant modified vaccinia virus Ankara, fowlpox virus, and non-replicating adenovirus. We have proceeded to test immunogenicity and efficacy of successful heterologous prime-boost vaccines in phase I/IIa trials in malaria naïve subjects in the UK and in semi-immune individuals in The Gambia. In these clinical trials, remarkably high levels of effector T-cell responses have been induced and significant protection documented in a human sporozoite challenge model. We summarize the preclinical design and development of these heterologous prime-boost vaccines and discuss the encouraging results that have been observed in vaccinated humans. |
| spellingShingle | Moore, A Hill, A Progress in DNA-based heterologous prime-boost immunization strategies for malaria. |
| title | Progress in DNA-based heterologous prime-boost immunization strategies for malaria. |
| title_full | Progress in DNA-based heterologous prime-boost immunization strategies for malaria. |
| title_fullStr | Progress in DNA-based heterologous prime-boost immunization strategies for malaria. |
| title_full_unstemmed | Progress in DNA-based heterologous prime-boost immunization strategies for malaria. |
| title_short | Progress in DNA-based heterologous prime-boost immunization strategies for malaria. |
| title_sort | progress in dna based heterologous prime boost immunization strategies for malaria |
| work_keys_str_mv | AT moorea progressindnabasedheterologousprimeboostimmunizationstrategiesformalaria AT hilla progressindnabasedheterologousprimeboostimmunizationstrategiesformalaria |