A delayed fractionated dose RTS,S AS01 vaccine regimen mediates protection via improved T follicular helper and B cell responses.
human
immunology
inflammation
malaria vaccine immunity
tfh and malaria vaccine
tfh, b cells and vaccine
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
29 04 2020
29 04 2020
Historique:
received:
15
09
2019
accepted:
14
04
2020
pubmed:
29
4
2020
medline:
10
4
2021
entrez:
29
4
2020
Statut:
epublish
Résumé
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 second dose that persisted after the third 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 third vaccine dose. We conclude that the DFD regimen favors persistence of functional B cells after the third dose.
Identifiants
pubmed: 32342859
doi: 10.7554/eLife.51889
pii: 51889
pmc: PMC7213985
doi:
pii:
Substances chimiques
Antibodies, Protozoan
0
Interleukins
0
Malaria Vaccines
0
interleukin-21
MKM3CA6LT1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Déclaration de conflit d'intérêts
SP, SC, PL, LP, UW, SP No competing interests declared, EJ is an employee of GSK, and owns shares of GSK
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