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

Marguerita Coccia, Cathérine Collignon, Cathérine Hervé, A. Chalon, I. Welsby, S. Detienne, M van Helden, S Dutta, C.J. Genito, N.C. Waters, K. Van Deun, A.K. Smilde, R.A. van den Berg, D. Franco, P. Bourguignon, Sandra Morel, N. Garçon, B.N. Lambrecht, S. Goriely, R. van der MostA.M. Didierlaurent

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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.
Original languageEnglish
Article number25
Journalnpj Vaccines
Volume2
DOIs
Publication statusPublished - 2017

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Lymph Nodes
Immunologic Adjuvants
Vaccine Immunogenicity
Ligands
QS 21

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Coccia, M., Collignon, C., Hervé, C., Chalon, A., Welsby, I., Detienne, S., ... Didierlaurent, A. M. (2017). Cellular and molecular synergy in AS01-adjuvanted vaccines results in an early IFNγ response promoting vaccine immunogenicity. npj Vaccines, 2, [25]. https://doi.org/10.1038/s41541-017-0027-3
Coccia, Marguerita ; Collignon, Cathérine ; Hervé, Cathérine ; 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, Sandra ; Garçon, N. ; Lambrecht, B.N. ; Goriely, S. ; van der Most, R. ; Didierlaurent, A.M. / Cellular and molecular synergy in AS01-adjuvanted vaccines results in an early IFNγ response promoting vaccine immunogenicity. In: npj Vaccines. 2017 ; Vol. 2.
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title = "Cellular and molecular synergy in AS01-adjuvanted vaccines results in an early IFNγ response promoting vaccine immunogenicity",
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.",
author = "Marguerita Coccia and Cath{\'e}rine Collignon and Cath{\'e}rine Herv{\'e} and A. Chalon and I. Welsby and S. Detienne and {van Helden}, M and S Dutta and C.J. Genito and N.C. Waters and {Van Deun}, K. and A.K. Smilde and {van den Berg}, R.A. and D. Franco and P. Bourguignon and Sandra Morel and N. Gar{\cc}on and B.N. Lambrecht and S. Goriely and {van der Most}, R. and A.M. Didierlaurent",
year = "2017",
doi = "10.1038/s41541-017-0027-3",
language = "English",
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Coccia, M, Collignon, C, Hervé, C, Chalon, A, Welsby, I, Detienne, S, van Helden, M, Dutta, S, Genito, CJ, Waters, NC, Van Deun, K, Smilde, AK, van den Berg, RA, Franco, D, Bourguignon, P, Morel, S, Garçon, N, Lambrecht, BN, Goriely, S, van der Most, R & Didierlaurent, AM 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

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.; Van Deun, K.; Smilde, A.K.; van den Berg, R.A.; Franco, D.; Bourguignon, P.; Morel, Sandra; Garçon, N.; Lambrecht, B.N.; Goriely, S.; van der Most, R.; Didierlaurent, A.M.

In: npj Vaccines, Vol. 2, 25, 2017.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Cellular and molecular synergy in AS01-adjuvanted vaccines results in an early IFNγ response promoting vaccine immunogenicity

AU - Coccia, Marguerita

AU - Collignon, Cathérine

AU - Hervé, Cathérine

AU - Chalon, A.

AU - Welsby, I.

AU - Detienne, S.

AU - van Helden, M

AU - Dutta, S

AU - Genito, C.J.

AU - Waters, N.C.

AU - Van Deun, K.

AU - Smilde, A.K.

AU - van den Berg, R.A.

AU - Franco, D.

AU - Bourguignon, P.

AU - Morel, Sandra

AU - Garçon, N.

AU - Lambrecht, B.N.

AU - Goriely, S.

AU - van der Most, R.

AU - Didierlaurent, A.M.

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

U2 - 10.1038/s41541-017-0027-3

DO - 10.1038/s41541-017-0027-3

M3 - Article

VL - 2

JO - npj Vaccines

JF - npj Vaccines

SN - 2059-0105

M1 - 25

ER -