Cellular immunity induced by the recombinant Plasmodium falciparum malaria vaccine, RTS,S/AS02, in semi-immune adults in The Gambia.
Vaccination of malaria-naive humans with recombinant RTS,S/AS02, which includes the C-terminus of the circumsporozoite protein (CS), has been shown to induce strong T cell responses to both the whole protein antigen and to peptides from CS. Here we show that strong T cell responses were also observe...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
2004
|
| _version_ | 1826289518306656256 |
|---|---|
| author | Pinder, M Reece, W Plebanski, M Akinwunmi, P Flanagan, K Lee, E Doherty, T Milligan, P Jaye, A Tornieporth, N Ballou, R McAdam, K Cohen, J Hill, A |
| author_facet | Pinder, M Reece, W Plebanski, M Akinwunmi, P Flanagan, K Lee, E Doherty, T Milligan, P Jaye, A Tornieporth, N Ballou, R McAdam, K Cohen, J Hill, A |
| author_sort | Pinder, M |
| collection | OXFORD |
| description | Vaccination of malaria-naive humans with recombinant RTS,S/AS02, which includes the C-terminus of the circumsporozoite protein (CS), has been shown to induce strong T cell responses to both the whole protein antigen and to peptides from CS. Here we show that strong T cell responses were also observed in a semi-immune population in The Gambia, West Africa. In a Phase I study, 20 adult male volunteers, lifelong residents in a malaria-endemic region, were given three doses of RTS,S/AS02 at 0, 1 and 6 months. Responses to RTS,S, hepatitis B surface antigen and peptides from CS were tested using lymphocyte proliferation, interferon (IFN)-gamma production in microcultures, and IFN-gamma ex vivo and cultured ELISPOT, before and after vaccination. Cytotoxic responses were tested only after vaccination and none were detected. Before vaccination, the majority of the volunteers (15/20) had detectable responses in at least one of the tests. After vaccination, responses increased in all assays except cytotoxicity. The increase was most marked for proliferation; all donors responded to RTS,S after the third dose and all except one donor responded to at least one peptide after the second or third dose. There was a lack of close association of peptide responses detected by the different assays, although in microcultures IFN-gamma responses were found only when proliferative responses were high, and responses by cultured ELISPOT and proliferation were found together more frequently after vaccination. We have therefore identified several peptide-specific T cell responses induced by RTS,S/AS02 which provides a mechanism to investigate potentially protective immune responses in the field. |
| first_indexed | 2024-03-07T02:30:05Z |
| format | Journal article |
| id | oxford-uuid:a6f20d69-d707-43b6-959b-42ad552b593f |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:30:05Z |
| publishDate | 2004 |
| record_format | dspace |
| spelling | oxford-uuid:a6f20d69-d707-43b6-959b-42ad552b593f2022-03-27T02:51:01ZCellular immunity induced by the recombinant Plasmodium falciparum malaria vaccine, RTS,S/AS02, in semi-immune adults in The Gambia.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:a6f20d69-d707-43b6-959b-42ad552b593fEnglishSymplectic Elements at Oxford2004Pinder, MReece, WPlebanski, MAkinwunmi, PFlanagan, KLee, EDoherty, TMilligan, PJaye, ATornieporth, NBallou, RMcAdam, KCohen, JHill, AVaccination of malaria-naive humans with recombinant RTS,S/AS02, which includes the C-terminus of the circumsporozoite protein (CS), has been shown to induce strong T cell responses to both the whole protein antigen and to peptides from CS. Here we show that strong T cell responses were also observed in a semi-immune population in The Gambia, West Africa. In a Phase I study, 20 adult male volunteers, lifelong residents in a malaria-endemic region, were given three doses of RTS,S/AS02 at 0, 1 and 6 months. Responses to RTS,S, hepatitis B surface antigen and peptides from CS were tested using lymphocyte proliferation, interferon (IFN)-gamma production in microcultures, and IFN-gamma ex vivo and cultured ELISPOT, before and after vaccination. Cytotoxic responses were tested only after vaccination and none were detected. Before vaccination, the majority of the volunteers (15/20) had detectable responses in at least one of the tests. After vaccination, responses increased in all assays except cytotoxicity. The increase was most marked for proliferation; all donors responded to RTS,S after the third dose and all except one donor responded to at least one peptide after the second or third dose. There was a lack of close association of peptide responses detected by the different assays, although in microcultures IFN-gamma responses were found only when proliferative responses were high, and responses by cultured ELISPOT and proliferation were found together more frequently after vaccination. We have therefore identified several peptide-specific T cell responses induced by RTS,S/AS02 which provides a mechanism to investigate potentially protective immune responses in the field. |
| spellingShingle | Pinder, M Reece, W Plebanski, M Akinwunmi, P Flanagan, K Lee, E Doherty, T Milligan, P Jaye, A Tornieporth, N Ballou, R McAdam, K Cohen, J Hill, A Cellular immunity induced by the recombinant Plasmodium falciparum malaria vaccine, RTS,S/AS02, in semi-immune adults in The Gambia. |
| title | Cellular immunity induced by the recombinant Plasmodium falciparum malaria vaccine, RTS,S/AS02, in semi-immune adults in The Gambia. |
| title_full | Cellular immunity induced by the recombinant Plasmodium falciparum malaria vaccine, RTS,S/AS02, in semi-immune adults in The Gambia. |
| title_fullStr | Cellular immunity induced by the recombinant Plasmodium falciparum malaria vaccine, RTS,S/AS02, in semi-immune adults in The Gambia. |
| title_full_unstemmed | Cellular immunity induced by the recombinant Plasmodium falciparum malaria vaccine, RTS,S/AS02, in semi-immune adults in The Gambia. |
| title_short | Cellular immunity induced by the recombinant Plasmodium falciparum malaria vaccine, RTS,S/AS02, in semi-immune adults in The Gambia. |
| title_sort | cellular immunity induced by the recombinant plasmodium falciparum malaria vaccine rts s as02 in semi immune adults in the gambia |
| work_keys_str_mv | AT pinderm cellularimmunityinducedbytherecombinantplasmodiumfalciparummalariavaccinertssas02insemiimmuneadultsinthegambia AT reecew cellularimmunityinducedbytherecombinantplasmodiumfalciparummalariavaccinertssas02insemiimmuneadultsinthegambia AT plebanskim cellularimmunityinducedbytherecombinantplasmodiumfalciparummalariavaccinertssas02insemiimmuneadultsinthegambia AT akinwunmip cellularimmunityinducedbytherecombinantplasmodiumfalciparummalariavaccinertssas02insemiimmuneadultsinthegambia AT flanagank cellularimmunityinducedbytherecombinantplasmodiumfalciparummalariavaccinertssas02insemiimmuneadultsinthegambia AT leee cellularimmunityinducedbytherecombinantplasmodiumfalciparummalariavaccinertssas02insemiimmuneadultsinthegambia AT dohertyt cellularimmunityinducedbytherecombinantplasmodiumfalciparummalariavaccinertssas02insemiimmuneadultsinthegambia AT milliganp cellularimmunityinducedbytherecombinantplasmodiumfalciparummalariavaccinertssas02insemiimmuneadultsinthegambia AT jayea cellularimmunityinducedbytherecombinantplasmodiumfalciparummalariavaccinertssas02insemiimmuneadultsinthegambia AT tornieporthn cellularimmunityinducedbytherecombinantplasmodiumfalciparummalariavaccinertssas02insemiimmuneadultsinthegambia AT ballour cellularimmunityinducedbytherecombinantplasmodiumfalciparummalariavaccinertssas02insemiimmuneadultsinthegambia AT mcadamk cellularimmunityinducedbytherecombinantplasmodiumfalciparummalariavaccinertssas02insemiimmuneadultsinthegambia AT cohenj cellularimmunityinducedbytherecombinantplasmodiumfalciparummalariavaccinertssas02insemiimmuneadultsinthegambia AT hilla cellularimmunityinducedbytherecombinantplasmodiumfalciparummalariavaccinertssas02insemiimmuneadultsinthegambia |