Cellular and molecular synergy in AS01-adjuvanted vaccines results in an early IFNγ response promoting vaccine immunogenicity

Margherita Coccia(GlaxoSmithKline (Belgium)), Catherine Collignon(GlaxoSmithKline (Belgium)), Caroline Hervé(GlaxoSmithKline (Belgium)), Aurélie Chalon(GlaxoSmithKline (Belgium)), Iain Welsby(Université Libre de Bruxelles), Sophie Detienne(Université Libre de Bruxelles), Mary J. van Helden(Vlaams Instituut voor Biotechnologie), Sheetij Dutta(Walter Reed Army Institute of Research), Christopher J. Genito(Walter Reed Army Institute of Research), Norman C. Waters(Walter Reed Army Institute of Research), Katrijn Van Deun(Tilburg University), Age K. Smilde(University of Amsterdam), Robert A. van den Berg(GlaxoSmithKline (Belgium)), David Franco(GlaxoSmithKline (Belgium)), Patricia Bourguignon(GlaxoSmithKline (Belgium)), Sandra Morel(GlaxoSmithKline (Belgium)), Nathalie Garçon(GlaxoSmithKline (Belgium)), Bart N. Lambrecht(Vlaams Instituut voor Biotechnologie), Stanislas Goriely(Université Libre de Bruxelles), Robbert van der Most(GlaxoSmithKline (Belgium)), Arnaud M. Didierlaurent(GlaxoSmithKline (Belgium))
npj Vaccines
August 17, 2017
10.1038/s41541-017-0027-3
Cited by 244Open Access
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Abstract

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.

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