CXCR3+ T follicular helper cells induced by co-administration of RTS,S/AS01B and viral vectored vaccines are associated with reduced immunogenicity and efficacy against Malaria
Malaria remains a significant cause of morbidity and mortality in sub-Saharan Africa. An efficacious vaccine will be an essential part of attempts to eradicate the disease. A vaccine strategy targeting multiple stages lifecycle stages may be required to achieve a high level of efficacy. In a series...
| Main Authors: | , , , , , , , |
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| Format: | Journal article |
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Frontiers Media
2018
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| _version_ | 1797095014645366784 |
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| author | Ewer (nee Russell), K Bowyer, G Grobbelaar, A Rampling, T Venkatraman, N Morelle, D Ballou, R Hill, A |
| author_facet | Ewer (nee Russell), K Bowyer, G Grobbelaar, A Rampling, T Venkatraman, N Morelle, D Ballou, R Hill, A |
| author_sort | Ewer (nee Russell), K |
| collection | OXFORD |
| description | Malaria remains a significant cause of morbidity and mortality in sub-Saharan Africa. An efficacious vaccine will be an essential part of attempts to eradicate the disease. A vaccine strategy targeting multiple stages lifecycle stages may be required to achieve a high level of efficacy. In a series of phase IIa clinical trials we tested different regimens of two vaccine platforms: RTS,S/AS01B, which induces antibody responses to target sporozoites and viral-vectored vaccines ChAd63-MVA ME-TRAP, which induce T cells that target infected hepatocytes. Concomitant administration of these vaccines significantly reduced humoral immunogenicity and protective efficacy against controlled human malaria infection. Strong Th1 cytokine responses induced by MVA ME-TRAP were associated with a skew in circulating T follicular helper cells towards a CXCR3+ phenotype and the observed reduction in antibody quantity and quality. This study illustrates that while a multistage-targeting vaccine strategy could provide high-level efficacy, the regimen design will require careful optimisation. |
| first_indexed | 2024-03-07T04:21:58Z |
| format | Journal article |
| id | oxford-uuid:cb51ac05-d30d-4030-9be4-044bc81a87ea |
| institution | University of Oxford |
| last_indexed | 2024-03-07T04:21:58Z |
| publishDate | 2018 |
| publisher | Frontiers Media |
| record_format | dspace |
| spelling | oxford-uuid:cb51ac05-d30d-4030-9be4-044bc81a87ea2022-03-27T07:13:59ZCXCR3+ T follicular helper cells induced by co-administration of RTS,S/AS01B and viral vectored vaccines are associated with reduced immunogenicity and efficacy against MalariaJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:cb51ac05-d30d-4030-9be4-044bc81a87eaSymplectic Elements at OxfordFrontiers Media2018Ewer (nee Russell), KBowyer, GGrobbelaar, ARampling, TVenkatraman, NMorelle, DBallou, RHill, AMalaria remains a significant cause of morbidity and mortality in sub-Saharan Africa. An efficacious vaccine will be an essential part of attempts to eradicate the disease. A vaccine strategy targeting multiple stages lifecycle stages may be required to achieve a high level of efficacy. In a series of phase IIa clinical trials we tested different regimens of two vaccine platforms: RTS,S/AS01B, which induces antibody responses to target sporozoites and viral-vectored vaccines ChAd63-MVA ME-TRAP, which induce T cells that target infected hepatocytes. Concomitant administration of these vaccines significantly reduced humoral immunogenicity and protective efficacy against controlled human malaria infection. Strong Th1 cytokine responses induced by MVA ME-TRAP were associated with a skew in circulating T follicular helper cells towards a CXCR3+ phenotype and the observed reduction in antibody quantity and quality. This study illustrates that while a multistage-targeting vaccine strategy could provide high-level efficacy, the regimen design will require careful optimisation. |
| spellingShingle | Ewer (nee Russell), K Bowyer, G Grobbelaar, A Rampling, T Venkatraman, N Morelle, D Ballou, R Hill, A CXCR3+ T follicular helper cells induced by co-administration of RTS,S/AS01B and viral vectored vaccines are associated with reduced immunogenicity and efficacy against Malaria |
| title | CXCR3+ T follicular helper cells induced by co-administration of RTS,S/AS01B and viral vectored vaccines are associated with reduced immunogenicity and efficacy against Malaria |
| title_full | CXCR3+ T follicular helper cells induced by co-administration of RTS,S/AS01B and viral vectored vaccines are associated with reduced immunogenicity and efficacy against Malaria |
| title_fullStr | CXCR3+ T follicular helper cells induced by co-administration of RTS,S/AS01B and viral vectored vaccines are associated with reduced immunogenicity and efficacy against Malaria |
| title_full_unstemmed | CXCR3+ T follicular helper cells induced by co-administration of RTS,S/AS01B and viral vectored vaccines are associated with reduced immunogenicity and efficacy against Malaria |
| title_short | CXCR3+ T follicular helper cells induced by co-administration of RTS,S/AS01B and viral vectored vaccines are associated with reduced immunogenicity and efficacy against Malaria |
| title_sort | cxcr3 t follicular helper cells induced by co administration of rts s as01b and viral vectored vaccines are associated with reduced immunogenicity and efficacy against malaria |
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