A statistical interaction between circumsporozoite protein-specific T cell and antibody responses and risk of clinical malaria episodes following vaccination with RTS,S/AS01E.
The candidate malaria vaccine RTS,S/AS01(E) provides significant but partial protection from clinical malaria. On in vitro circumsporozoite protein (CSP) peptide stimulation and intra-cellular cytokine staining of whole blood taken from 407 5-17 month-old children in a phase IIb trial of RTS,S/AS01(...
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0052870&type=printable |
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| author | Francis M Ndungu Jedidah Mwacharo Domtila Kimani Oscar Kai Philippe Moris Erik Jongert Johan Vekemans Ally Olotu Philip Bejon |
| author_facet | Francis M Ndungu Jedidah Mwacharo Domtila Kimani Oscar Kai Philippe Moris Erik Jongert Johan Vekemans Ally Olotu Philip Bejon |
| author_sort | Francis M Ndungu |
| collection | DOAJ |
| description | The candidate malaria vaccine RTS,S/AS01(E) provides significant but partial protection from clinical malaria. On in vitro circumsporozoite protein (CSP) peptide stimulation and intra-cellular cytokine staining of whole blood taken from 407 5-17 month-old children in a phase IIb trial of RTS,S/AS01(E), we identified significantly increased frequencies of two CSP-specific CD4+ T cells phenotypes among RTS,S/AS01(E) vaccinees (IFNγ-IL2+TNF- and IFNγ-IL2+TNF+ CD4+ T cells), and increased frequency of IFNγ-IL2-TNF+ CD4+ T cells after natural exposure. All these T cells phenotypes were individually associated with reductions in the risk of clinical malaria, but IFNγ-IL2-TNF+ CD4+ T cells independently predicted reduced risk of clinical malaria on multi-variable analysis (HR = 0.29, 95% confidence intervals 0.15-0.54, p<0.0005). Furthermore, there was a strongly significant synergistic interaction between CSP-specific IFNγ-IL2-TNF+ CD4+ T cells and anti-CSP antibodies in determining protection against clinical malaria (p = 0.002). Vaccination strategies that combine potent cellular and antibody responses may enhance protection against malaria. |
| format | Article |
| id | doaj-art-d4d14fae23c945c3b3f5c32a1b4ed52e |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-d4d14fae23c945c3b3f5c32a1b4ed52e2025-08-20T02:30:50ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01712e5287010.1371/journal.pone.0052870A statistical interaction between circumsporozoite protein-specific T cell and antibody responses and risk of clinical malaria episodes following vaccination with RTS,S/AS01E.Francis M NdunguJedidah MwacharoDomtila KimaniOscar KaiPhilippe MorisErik JongertJohan VekemansAlly OlotuPhilip BejonThe candidate malaria vaccine RTS,S/AS01(E) provides significant but partial protection from clinical malaria. On in vitro circumsporozoite protein (CSP) peptide stimulation and intra-cellular cytokine staining of whole blood taken from 407 5-17 month-old children in a phase IIb trial of RTS,S/AS01(E), we identified significantly increased frequencies of two CSP-specific CD4+ T cells phenotypes among RTS,S/AS01(E) vaccinees (IFNγ-IL2+TNF- and IFNγ-IL2+TNF+ CD4+ T cells), and increased frequency of IFNγ-IL2-TNF+ CD4+ T cells after natural exposure. All these T cells phenotypes were individually associated with reductions in the risk of clinical malaria, but IFNγ-IL2-TNF+ CD4+ T cells independently predicted reduced risk of clinical malaria on multi-variable analysis (HR = 0.29, 95% confidence intervals 0.15-0.54, p<0.0005). Furthermore, there was a strongly significant synergistic interaction between CSP-specific IFNγ-IL2-TNF+ CD4+ T cells and anti-CSP antibodies in determining protection against clinical malaria (p = 0.002). Vaccination strategies that combine potent cellular and antibody responses may enhance protection against malaria.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0052870&type=printable |
| spellingShingle | Francis M Ndungu Jedidah Mwacharo Domtila Kimani Oscar Kai Philippe Moris Erik Jongert Johan Vekemans Ally Olotu Philip Bejon A statistical interaction between circumsporozoite protein-specific T cell and antibody responses and risk of clinical malaria episodes following vaccination with RTS,S/AS01E. PLoS ONE |
| title | A statistical interaction between circumsporozoite protein-specific T cell and antibody responses and risk of clinical malaria episodes following vaccination with RTS,S/AS01E. |
| title_full | A statistical interaction between circumsporozoite protein-specific T cell and antibody responses and risk of clinical malaria episodes following vaccination with RTS,S/AS01E. |
| title_fullStr | A statistical interaction between circumsporozoite protein-specific T cell and antibody responses and risk of clinical malaria episodes following vaccination with RTS,S/AS01E. |
| title_full_unstemmed | A statistical interaction between circumsporozoite protein-specific T cell and antibody responses and risk of clinical malaria episodes following vaccination with RTS,S/AS01E. |
| title_short | A statistical interaction between circumsporozoite protein-specific T cell and antibody responses and risk of clinical malaria episodes following vaccination with RTS,S/AS01E. |
| title_sort | statistical interaction between circumsporozoite protein specific t cell and antibody responses and risk of clinical malaria episodes following vaccination with rts s as01e |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0052870&type=printable |
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