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Peer-reviewedCC BY 4.0NPJ Vaccines

Modeling time-varying efficacy of RTS,S/AS01 malaria vaccine across trial settings

  • Ziwei Zhao1
  • Paul Milligan2
  • Yin Bun Cheung1,3,4
4 affiliations
  1. 1Centre for Biomedical Data Science, Duke-NUS Medical School, National University of Singapore, Singapore, Singapore
  2. 2Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, UK
  3. 3Signature Programme in Health Services & Systems Research, Duke-NUS Medical School, Singapore, Singapore
  4. 4Tampere Center for Child, Adolescent and Maternal Health Research, Tampere University, Tampere, Finland
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Abstract

Correctly evaluating how vaccine efficacy (VE) changes over time is important for understanding long-term protection and guiding vaccination strategies. Using the 18-month pre-booster data from the multi-center RTS,S/AS01 malaria vaccine trial, we examined how different approaches of modeling time-varying VE affect the interpretation of vaccine protection. Four commonly used linear-in-parameter functions and a four-parameter monotonic function were evaluated and compared with semi-parametric spline benchmarks. Across study sites, the four-parameter function was favored when a sufficient number of clinical malaria episodes were observed. Different VE specifications led to substantially different estimates of vaccine impact under a seasonal delivery strategy. Across settings with a sufficient number of episodes, the four-parameter model recovered an inverse-sigmoid pattern of RTS,S/AS01 protection over 18 months, with rapid early decline followed by stabilization at 20-40%. These findings show that modeling choices influence interpretation of vaccine protection and support the four-parameter approach as a parsimonious, biologically-interpretable parametric form for characterizing waning VE in the RTS,S/AS01 setting, with broader applicability across other vaccine platforms requiring further evaluation.

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Cite

BibTeXRIS
BibTeX
@article{zhao2026modeling,
  title = {{Modeling time-varying efficacy of RTS,S/AS01 malaria vaccine across trial settings}},
  author = {Ziwei Zhao and Paul Milligan and Yin Bun Cheung},
  journal = {NPJ Vaccines},
  year = {2026},
  month = jul,
  doi = {10.1038/s41541-026-01519-4},
  url = {https://doi.org/10.1038/s41541-026-01519-4},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Modeling time-varying efficacy of RTS,S/AS01 malaria vaccine across trial settings
AU  - Ziwei Zhao
AU  - Paul Milligan
AU  - Yin Bun Cheung
PY  - 2026
DA  - 2026/07/03
JO  - NPJ Vaccines
DO  - 10.1038/s41541-026-01519-4
UR  - https://doi.org/10.1038/s41541-026-01519-4
AB  - Correctly evaluating how vaccine efficacy (VE) changes over time is important for understanding long-term protection and guiding vaccination strategies. Using the 18-month pre-booster data from the multi-center RTS,S/AS01 malaria vaccine trial, we examined how different approaches of modeling time-varying VE affect the interpretation of vaccine protection. Four commonly used linear-in-parameter functions and a four-parameter monotonic function were evaluated and compared with semi-parametric spline benchmarks. Across study sites, the four-parameter function was favored when a sufficient number of clinical malaria episodes were observed. Different VE specifications led to substantially different estimates of vaccine impact under a seasonal delivery strategy. Across settings with a sufficient number of episodes, the four-parameter model recovered an inverse-sigmoid pattern of RTS,S/AS01 protection over 18 months, with rapid early decline followed by stabilization at 20-40%. These findings show that modeling choices influence interpretation of vaccine protection and support the four-parameter approach as a parsimonious, biologically-interpretable parametric form for characterizing waning VE in the RTS,S/AS01 setting, with broader applicability across other vaccine platforms requiring further evaluation.
SN  - 2059-0105
ER  -