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Cellular and molecular synergy in AS01-adjuvanted vaccines results in an early IFNγ response promoting vaccine immunogenicity
Coccia,Marguerita Collignon,Cathérine Hervé,Cathérine Chalon,A. Welsby,I. Detienne,S. van Helden,M Dutta,S Genito,C.J. Waters,N.C.
Coccia,Marguerita
Collignon,Cathérine
Hervé,Cathérine
Chalon,A.
Welsby,I.
Detienne,S.
van Helden,M
Dutta,S
Genito,C.J.
Waters,N.C.
Abstract
Combining immunostimulants in adjuvants can improve the quality of the immune response to vaccines. Here, we report a unique mechanism of molecular and cellular synergy between a TLR4 ligand, 3-O-desacyl-4’-monophosphoryl lipid A (MPL), and a saponin, QS-21, the constituents of the Adjuvant System AS01. AS01 is part of the malaria and herpes zoster vaccine candidates that have demonstrated efficacy in phase III studies. Hours after injection of AS01-adjuvanted vaccine, resident cells, such as NK cells and CD8+ T cells, release IFNγ in the lymph node draining the injection site. This effect results from MPL and QS-21 synergy and is controlled by macrophages, IL-12 and IL-18. Depletion strategies showed that this early IFNγ production was essential for the activation of dendritic cells and the development of Th1 immunity by AS01-adjuvanted vaccine. A similar activation was observed in the lymph node of AS01-injected macaques as well as in the blood of individuals receiving the malaria RTS,S vaccine. This mechanism, previously described for infections, illustrates how adjuvants trigger naturally occurring pathways to improve the efficacy of vaccines.
Description
Date
2017
Journal Title
Journal ISSN
Volume Title
Publisher
Research Projects
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Keywords
SDG 3 - Good Health and Well-being
Citation
Coccia, M, Collignon, C, Hervé, C, Chalon, A, Welsby, I, Detienne, S, van Helden, M, Dutta, S, Genito, C J, Waters, N C, Van Deun, K, Smilde, A K, van den Berg, R A, Franco, D, Bourguignon, P, Morel, S, Garçon, N, Lambrecht, B N, Goriely, S, van der Most, R & Didierlaurent, A M 2017, 'Cellular and molecular synergy in AS01-adjuvanted vaccines results in an early IFNγ response promoting vaccine immunogenicity', npj Vaccines, vol. 2, 25. https://doi.org/10.1038/s41541-017-0027-3
License
info:eu-repo/semantics/openAccess