In this section
@article{Hogan:2018:10.1186/s12916-018-1095-6,
author = {Hogan, AB and Winskill, P and Verity, R and Griffin, J and Ghani, A},
doi = {10.1186/s12916-018-1095-6},
journal = {BMC Medicine},
title = {Modelling population-level impact to inform target product profiles for childhood malaria vaccines},
url = {http://dx.doi.org/10.1186/s12916-018-1095-6},
volume = {16},
year = {2018}
}
TY - JOUR
AB - BackgroundThe 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.MethodsWe 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.ResultsIn 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.ConclusionsOur 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 outpe
AU - Hogan,AB
AU - Winskill,P
AU - Verity,R
AU - Griffin,J
AU - Ghani,A
DO - 10.1186/s12916-018-1095-6
PY - 2018///
SN - 1741-7015
TI - Modelling population-level impact to inform target product profiles for childhood malaria vaccines
T2 - BMC Medicine
UR - http://dx.doi.org/10.1186/s12916-018-1095-6
UR - http://hdl.handle.net/10044/1/61057
VL - 16
ER -
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