Journal article
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
- Abstract:
- 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.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, pdf, 5.9MB, Terms of use)
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- Publisher copy:
- 10.3389/fimmu.2018.01660
Authors
- Publisher:
- Frontiers Media
- Journal:
- Frontiers in Immunology More from this journal
- Volume:
- 9
- Pages:
- 1660
- Publication date:
- 2018-07-30
- Acceptance date:
- 2018-07-04
- DOI:
- EISSN:
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1664-3224
- Keywords:
- Pubs id:
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pubs:864370
- UUID:
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uuid:cb51ac05-d30d-4030-9be4-044bc81a87ea
- Local pid:
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pubs:864370
- Deposit date:
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2018-07-04
- ARK identifier:
Terms of use
- Copyright holder:
- Bowyer et al
- Copyright date:
- 2018
- Notes:
- © 2018 Bowyer, Grobbelaar, Rampling, Venkatraman, Morelle, Ballou, Hill and Ewer. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
- Licence:
- CC Attribution (CC BY)
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