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dc.contributor.authorHogan, ABen_US
dc.contributor.authorWinskill, Pen_US
dc.contributor.authorVerity, Ren_US
dc.contributor.authorGriffin, JTen_US
dc.contributor.authorGhani, ACen_US
dc.date.accessioned2018-08-08T09:45:49Z
dc.date.available2018-06-05en_US
dc.date.issued2018-07-13en_US
dc.date.submitted2018-08-05T11:28:10.936Z
dc.identifier.urihttp://qmro.qmul.ac.uk/xmlui/handle/123456789/43125
dc.description.abstractBACKGROUND: The RTS,S/AS01 vaccine for Plasmodium falciparum malaria demonstrated moderate efficacy in 5-17-month-old children in phase 3 trials, and from 2018, the vaccine will be evaluated through a large-scale pilot implementation program. Work is ongoing to optimise this vaccine, with higher efficacy for a different schedule demonstrated in a phase 2a challenge study. The objective of our study was to investigate the population-level impact of a modified RTS,S/AS01 schedule and dose amount in order to inform the target product profile for a second-generation malaria vaccine. METHODS: We used a mathematical modelling approach as the basis for our study. We simulated the changing anti-circumsporozoite antibody titre following vaccination and related the titre to vaccine efficacy. We then implemented this efficacy profile within an individual-based model of malaria transmission. We compared initial efficacy, duration and dose timing, and evaluated the potential public health impact of a modified vaccine in children aged 5-17 months, measuring clinical cases averted in children younger than 5 years. RESULTS: In the first decade of delivery, initial efficacy was associated with a higher reduction in childhood clinical cases compared to vaccine duration. This effect was more pronounced in high transmission settings and was due to the efficacy benefit occurring in younger ages where disease burden is highest. However, the low initial efficacy and long duration schedule averted more cases across all age cohorts if a longer time horizon was considered. We observed an age-shifting effect due to the changing immunological profile in higher transmission settings, in scenarios where initial efficacy was higher, and the fourth dose administered earlier. CONCLUSIONS: Our findings indicate that, for an imperfect childhood malaria vaccine with suboptimal efficacy, it may be advantageous to prioritise initial efficacy over duration. We predict that a modified vaccine could outperform the current RTS,S/AS01, although fourth dose timing will affect the age group that derives the greatest benefit. Further, the outcome measure and timeframe over which a vaccine is assessed are important when prioritising vaccine elements. This study provides insight into the most important characteristics of a malaria vaccine for at-risk groups and shows how distinct vaccine properties translate to public health outcomes. These findings may be used to prioritise target product profile elements for second-generation childhood malaria vaccines.en_US
dc.description.sponsorshipThis work was funded by a grant from PATH. RV acknowledges fellowship support from the UK Medical Research Council, and PW and ACG acknowledge support from the Bill & Melinda Gates Foundation. We additionally acknowledge Centre support from the UK Medical Research Council and Department for International Development under the MRC/DfID concordat. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.en_US
dc.format.extent109 - ?en_US
dc.languageengen_US
dc.relation.ispartofBMC Meden_US
dc.rightsThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
dc.subjectEfficacyen_US
dc.subjectMalariaen_US
dc.subjectPlasmodium falciparumen_US
dc.subjectRTS,S/AS01en_US
dc.subjectSecond-generation malaria vaccineen_US
dc.subjectTarget product profileen_US
dc.subjectChilden_US
dc.subjectChild, Preschoolen_US
dc.subjectFemaleen_US
dc.subjectHumansen_US
dc.subjectInfanten_US
dc.subjectMalariaen_US
dc.subjectMalaria Vaccinesen_US
dc.subjectTime Factorsen_US
dc.titleModelling population-level impact to inform target product profiles for childhood malaria vaccines.en_US
dc.typeArticle
dc.rights.holder© The Author(s). 2018
dc.identifier.doi10.1186/s12916-018-1095-6en_US
pubs.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/30001708en_US
pubs.issue1en_US
pubs.notesNo embargoen_US
pubs.publication-statusPublished onlineen_US
pubs.volume16en_US
dcterms.dateAccepted2018-06-05en_US
qmul.funderModelling the public health impact and cost-effectiveness of the RTS,S malaria vaccine in malaria endemic countries::PATH-Program for Appropriate Technology in Healthen_US


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