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

Margherita Coccia, Catherine Collignon, Caroline Hervé, Aurélie Chalon, Iain Welsby, Sophie Detienne, Mary van Helden (UGent) , Sheetij Dutta, Christopher J Genito, Norman C Waters, et al.
(2017) NPJ VACCINES. 2(1).
Author
Organization
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.
Keywords
FALCIPARUM CIRCUMSPOROZOITE PROTEIN, NK CELLS, T-CELLS, IMMUNE-RESPONSE, DENDRITIC CELLS, LYMPH-NODES, INFLUENZA VACCINATION, HOST-DEFENSE, MICE, PROTECTION

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Citation

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MLA
Coccia, Margherita, et al. “Cellular and Molecular Synergy in AS01-Adjuvanted Vaccines Results in an Early IFNγ Response Promoting Vaccine Immunogenicity.” NPJ VACCINES, vol. 2, no. 1, 2017, doi:10.1038/s41541-017-0027-3.
APA
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(1). https://doi.org/10.1038/s41541-017-0027-3
Chicago author-date
Coccia, Margherita, Catherine Collignon, Caroline Hervé, Aurélie Chalon, Iain Welsby, Sophie Detienne, Mary van Helden, et al. 2017. “Cellular and Molecular Synergy in AS01-Adjuvanted Vaccines Results in an Early IFNγ Response Promoting Vaccine Immunogenicity.” NPJ VACCINES 2 (1). https://doi.org/10.1038/s41541-017-0027-3.
Chicago author-date (all authors)
Coccia, Margherita, Catherine Collignon, Caroline Hervé, Aurélie Chalon, Iain Welsby, Sophie Detienne, Mary van Helden, Sheetij Dutta, Christopher J Genito, Norman C Waters, Katrijn Van Deun, Age K Smilde, Robert A van den Berg, David Franco, Patricia Bourguignon, Sandra Morel, Nathalie Garçon, Bart Lambrecht, Stanislas Goriely, Robbert van der Most, and Arnaud M Didierlaurent. 2017. “Cellular and Molecular Synergy in AS01-Adjuvanted Vaccines Results in an Early IFNγ Response Promoting Vaccine Immunogenicity.” NPJ VACCINES 2 (1). doi:10.1038/s41541-017-0027-3.
Vancouver
1.
Coccia M, Collignon C, Hervé C, Chalon A, Welsby I, Detienne S, et al. Cellular and molecular synergy in AS01-adjuvanted vaccines results in an early IFNγ response promoting vaccine immunogenicity. NPJ VACCINES. 2017;2(1).
IEEE
[1]
M. Coccia et al., “Cellular and molecular synergy in AS01-adjuvanted vaccines results in an early IFNγ response promoting vaccine immunogenicity,” NPJ VACCINES, vol. 2, no. 1, 2017.
@article{8556284,
  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.}},
  articleno    = {{25}},
  author       = {{Coccia, Margherita and Collignon, Catherine and Hervé, Caroline and Chalon, Aurélie and Welsby, Iain and Detienne, Sophie and van Helden, Mary and Dutta, Sheetij and Genito, Christopher J and Waters, Norman C and Van Deun, Katrijn and Smilde, Age K and van den Berg, Robert A and Franco, David and Bourguignon, Patricia and Morel, Sandra and Garçon, Nathalie and Lambrecht, Bart and Goriely, Stanislas and van der Most, Robbert and Didierlaurent, Arnaud M}},
  issn         = {{2059-0105}},
  journal      = {{NPJ VACCINES}},
  keywords     = {{FALCIPARUM CIRCUMSPOROZOITE PROTEIN,NK CELLS,T-CELLS,IMMUNE-RESPONSE,DENDRITIC CELLS,LYMPH-NODES,INFLUENZA VACCINATION,HOST-DEFENSE,MICE,PROTECTION}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{14}},
  title        = {{Cellular and molecular synergy in AS01-adjuvanted vaccines results in an early IFNγ response promoting vaccine immunogenicity}},
  url          = {{http://doi.org/10.1038/s41541-017-0027-3}},
  volume       = {{2}},
  year         = {{2017}},
}
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