Delayed fractional dose regimen of the RTS,S/AS01 malaria vaccine candidate enhances an IgG4 response that inhibits serum opsonophagocytosis

Delayed fractional dose regimen of the RTS,S/AS01 malaria vaccine candidate enhances an IgG4 response that inhibits serum opsonophagocytosis

Abstract A recent study of the RTS,S malaria vaccine, which is based on the circumsporozoite protein (CSP), demonstrated an increase in efficacy from 50–60% to 80% when using a delayed fractional dose regimen, in which the standard 0–1–2 month immunization schedule was modified to a 0–1–7 month sche...

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Autores principales: Sidhartha Chaudhury, Jason A. Regules, Christian A. Darko, Sheetij Dutta, Anders Wallqvist, Norman C. Waters, Erik Jongert, Franck Lemiale, Elke S. Bergmann-Leitner
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Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/da43572f2ab14d5da906e3ca77074fd9
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spelling oai:doaj.org-article:da43572f2ab14d5da906e3ca77074fd92021-12-02T15:05:30ZDelayed fractional dose regimen of the RTS,S/AS01 malaria vaccine candidate enhances an IgG4 response that inhibits serum opsonophagocytosis10.1038/s41598-017-08526-52045-2322https://doaj.org/article/da43572f2ab14d5da906e3ca77074fd92017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08526-5https://doaj.org/toc/2045-2322Abstract A recent study of the RTS,S malaria vaccine, which is based on the circumsporozoite protein (CSP), demonstrated an increase in efficacy from 50–60% to 80% when using a delayed fractional dose regimen, in which the standard 0–1–2 month immunization schedule was modified to a 0–1–7 month schedule and the third immunization was delivered at 20% of the full dose. Given the role that antibodies can play in RTS,S-induced protection, we sought to determine how the modified regimen alters IgG subclasses and serum opsonophagocytic activity (OPA). Previously, we showed that lower CSP-mediated OPA was associated with protection in an RTS,S study. Here we report that the delayed fractional dose regimen resulted in decreased CSP-mediated OPA and an enhanced CSP-specific IgG4 response. Linear regression modeling predicted that CSP-specific IgG1 promote OPA, and that CSP-specific IgG4 interferes with OPA, which we subsequently confirmed by IgG subclass depletion. Although the role of IgG4 antibodies and OPA in protection is still unclear, our findings, combined with previous results that the delayed fractional dose increases CSP-specific antibody avidity and somatic hypermutation frequency in CSP-specific B cells, demonstrate how changes in vaccine regimen alone can significantly alter the quality of antibody responses to improve vaccine efficacy.Sidhartha ChaudhuryJason A. RegulesChristian A. DarkoSheetij DuttaAnders WallqvistNorman C. WatersErik JongertFranck LemialeElke S. Bergmann-LeitnerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Sidhartha Chaudhury
Jason A. Regules
Christian A. Darko
Sheetij Dutta
Anders Wallqvist
Norman C. Waters
Erik Jongert
Franck Lemiale
Elke S. Bergmann-Leitner
Delayed fractional dose regimen of the RTS,S/AS01 malaria vaccine candidate enhances an IgG4 response that inhibits serum opsonophagocytosis
description Abstract A recent study of the RTS,S malaria vaccine, which is based on the circumsporozoite protein (CSP), demonstrated an increase in efficacy from 50–60% to 80% when using a delayed fractional dose regimen, in which the standard 0–1–2 month immunization schedule was modified to a 0–1–7 month schedule and the third immunization was delivered at 20% of the full dose. Given the role that antibodies can play in RTS,S-induced protection, we sought to determine how the modified regimen alters IgG subclasses and serum opsonophagocytic activity (OPA). Previously, we showed that lower CSP-mediated OPA was associated with protection in an RTS,S study. Here we report that the delayed fractional dose regimen resulted in decreased CSP-mediated OPA and an enhanced CSP-specific IgG4 response. Linear regression modeling predicted that CSP-specific IgG1 promote OPA, and that CSP-specific IgG4 interferes with OPA, which we subsequently confirmed by IgG subclass depletion. Although the role of IgG4 antibodies and OPA in protection is still unclear, our findings, combined with previous results that the delayed fractional dose increases CSP-specific antibody avidity and somatic hypermutation frequency in CSP-specific B cells, demonstrate how changes in vaccine regimen alone can significantly alter the quality of antibody responses to improve vaccine efficacy.
format article
author Sidhartha Chaudhury
Jason A. Regules
Christian A. Darko
Sheetij Dutta
Anders Wallqvist
Norman C. Waters
Erik Jongert
Franck Lemiale
Elke S. Bergmann-Leitner
author_facet Sidhartha Chaudhury
Jason A. Regules
Christian A. Darko
Sheetij Dutta
Anders Wallqvist
Norman C. Waters
Erik Jongert
Franck Lemiale
Elke S. Bergmann-Leitner
author_sort Sidhartha Chaudhury
title Delayed fractional dose regimen of the RTS,S/AS01 malaria vaccine candidate enhances an IgG4 response that inhibits serum opsonophagocytosis
title_short Delayed fractional dose regimen of the RTS,S/AS01 malaria vaccine candidate enhances an IgG4 response that inhibits serum opsonophagocytosis
title_full Delayed fractional dose regimen of the RTS,S/AS01 malaria vaccine candidate enhances an IgG4 response that inhibits serum opsonophagocytosis
title_fullStr Delayed fractional dose regimen of the RTS,S/AS01 malaria vaccine candidate enhances an IgG4 response that inhibits serum opsonophagocytosis
title_full_unstemmed Delayed fractional dose regimen of the RTS,S/AS01 malaria vaccine candidate enhances an IgG4 response that inhibits serum opsonophagocytosis
title_sort delayed fractional dose regimen of the rts,s/as01 malaria vaccine candidate enhances an igg4 response that inhibits serum opsonophagocytosis
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/da43572f2ab14d5da906e3ca77074fd9
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