A delayed fractionated dose RTS,S AS01 vaccine regimen mediates protection via improved T follicular helper and B cell responses
- University of Miami Miller School of Medicine, United States
- Biotechnology HPC Software Applications Institute, U.S. Army Medical Research and Materiel Command, United States
- GSK Vaccine, Belgium
- PATH's Malaria Vaccine Initiative, United States
- University of Miami Miller School of Medicine, United States
Abstract
Malaria-071, a controlled human malaria infection trial, demonstrated that administration of three doses of RTS,S/AS01 malaria vaccine given at one month intervals was inferior to a delayed fractional dose (DFD) schedule (62.5% vs 86.7% protection respectively). To investigate the underlying immunologic mechanism, we analyzed the B and T peripheral follicular helper cell (pTfh) responses. Here we show that protection in both study arms was associated with early induction of functional IL-21-secreting circumsporozoite (CSP)-specific pTfh cells together with induction of CSP-specific memory B cell responses after the 2nd dose that persisted after the 3rd dose. Data integration of key immunologic measures identified a subset of non-protected individuals in the standard (STD) vaccine arm who lost prior protective B cell responses after receiving the 3rd vaccine dose. We conclude that the DFD regimen favors persistence of functional B cells post 3rd dose.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 2, 3, 4 and 5
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Funding
Program for Appropriate Technology in Health
- Savita Pahwa
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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A delayed fractionated dose RTS,S AS01 vaccine regimen mediates protection via improved T follicular helper and B cell responses
eLife 9:e51889.
https://doi.org/10.7554/eLife.51889
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