A Plasmodium falciparum candidate vaccine based on a six-antigen polyprotein encoded by recombinant poxviruses.
To generate broadly protective T cell responses more similar to those acquired after vaccination with radiation-attenuated Plasmodium falciparum sporozoites, we have constructed candidate subunit malaria vaccines expressing six preerythrocytic antigens linked together to produce a 3240-aa-long polyp...
| Main Authors: | , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2004
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| _version_ | 1826301475094003712 |
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| author | Prieur, E Gilbert, S Schneider, J Moore, A Sheu, E Goonetilleke, N Robson, K Hill, A |
| author_facet | Prieur, E Gilbert, S Schneider, J Moore, A Sheu, E Goonetilleke, N Robson, K Hill, A |
| author_sort | Prieur, E |
| collection | OXFORD |
| description | To generate broadly protective T cell responses more similar to those acquired after vaccination with radiation-attenuated Plasmodium falciparum sporozoites, we have constructed candidate subunit malaria vaccines expressing six preerythrocytic antigens linked together to produce a 3240-aa-long polyprotein (L3SEPTL). This polyprotein was expressed by a plasmid DNA vaccine vector (DNA) and by two attenuated poxvirus vectors, modified vaccinia virus Ankara (MVA) and fowlpox virus of the FP9 strain. MVAL3SEPTL boosted anti-thrombospondin-related adhesive protein (anti-TRAP) and anti-liver stage antigen 1 (anti-LSA1) CD8(+) T cell responses when primed by single antigen TRAP- or LSA1-expressing DNAs, respectively, but not by DNA-L3SEPTL. However, prime boost regimes involving two heterologous viral vectors expressing L3SEPTL induced a strong cellular response directed against an LSA1 peptide located in the C-terminal region of the polyprotein. Peptide-specific T cells secreted IFN-gamma and were cytotoxic. IFN-gamma-secreting T cells specific for each of the six antigens were induced after vaccination with L3SEPTL, supporting the use of polyprotein inserts to induce multispecific T cells against P. falciparum. The use of polyprotein constructs in nonreplicating poxviruses should broaden the target antigen range of vaccine-induced immunity and increase the number of potential epitopes available for immunogenetically diverse human populations. |
| first_indexed | 2024-03-07T05:32:59Z |
| format | Journal article |
| id | oxford-uuid:e2e7b99d-4915-4b3c-b3f5-0b50abe31dee |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:32:59Z |
| publishDate | 2004 |
| record_format | dspace |
| spelling | oxford-uuid:e2e7b99d-4915-4b3c-b3f5-0b50abe31dee2022-03-27T10:04:56ZA Plasmodium falciparum candidate vaccine based on a six-antigen polyprotein encoded by recombinant poxviruses.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e2e7b99d-4915-4b3c-b3f5-0b50abe31deeEnglishSymplectic Elements at Oxford2004Prieur, EGilbert, SSchneider, JMoore, ASheu, EGoonetilleke, NRobson, KHill, ATo generate broadly protective T cell responses more similar to those acquired after vaccination with radiation-attenuated Plasmodium falciparum sporozoites, we have constructed candidate subunit malaria vaccines expressing six preerythrocytic antigens linked together to produce a 3240-aa-long polyprotein (L3SEPTL). This polyprotein was expressed by a plasmid DNA vaccine vector (DNA) and by two attenuated poxvirus vectors, modified vaccinia virus Ankara (MVA) and fowlpox virus of the FP9 strain. MVAL3SEPTL boosted anti-thrombospondin-related adhesive protein (anti-TRAP) and anti-liver stage antigen 1 (anti-LSA1) CD8(+) T cell responses when primed by single antigen TRAP- or LSA1-expressing DNAs, respectively, but not by DNA-L3SEPTL. However, prime boost regimes involving two heterologous viral vectors expressing L3SEPTL induced a strong cellular response directed against an LSA1 peptide located in the C-terminal region of the polyprotein. Peptide-specific T cells secreted IFN-gamma and were cytotoxic. IFN-gamma-secreting T cells specific for each of the six antigens were induced after vaccination with L3SEPTL, supporting the use of polyprotein inserts to induce multispecific T cells against P. falciparum. The use of polyprotein constructs in nonreplicating poxviruses should broaden the target antigen range of vaccine-induced immunity and increase the number of potential epitopes available for immunogenetically diverse human populations. |
| spellingShingle | Prieur, E Gilbert, S Schneider, J Moore, A Sheu, E Goonetilleke, N Robson, K Hill, A A Plasmodium falciparum candidate vaccine based on a six-antigen polyprotein encoded by recombinant poxviruses. |
| title | A Plasmodium falciparum candidate vaccine based on a six-antigen polyprotein encoded by recombinant poxviruses. |
| title_full | A Plasmodium falciparum candidate vaccine based on a six-antigen polyprotein encoded by recombinant poxviruses. |
| title_fullStr | A Plasmodium falciparum candidate vaccine based on a six-antigen polyprotein encoded by recombinant poxviruses. |
| title_full_unstemmed | A Plasmodium falciparum candidate vaccine based on a six-antigen polyprotein encoded by recombinant poxviruses. |
| title_short | A Plasmodium falciparum candidate vaccine based on a six-antigen polyprotein encoded by recombinant poxviruses. |
| title_sort | plasmodium falciparum candidate vaccine based on a six antigen polyprotein encoded by recombinant poxviruses |
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