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CCR2-and Flt3-dependent inflammatory conventional type 2 dendritic cells are necessary for the induction of adaptive immunity by the human vaccine adjuvant system AS01

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Abstract
The Adjuvant System AS01 contains monophosphoryl lipid A (MPL) and the saponin QS-21 in a liposomal formulation. AS01 is included in recently developed vaccines against malaria and varicella zoster virus. Like for many other adjuvants, induction of adaptive immunity by AS01 is highly dependent on the ability to recruit and activate dendritic cells (DCs) that migrate to the draining lymph node for T and B cell stimulation. The objective of this study was to more precisely address the contribution of the different conventional (cDC) and monocyte-derived DC (MC) subsets in the orchestration of the adaptive immune response after immunization with AS01 adjuvanted vaccine. The combination of MPL and QS-21 in AS01 induced strong recruitment of CD26(+)XCR1(+) cDC1s, CD26(+)CD172(+) cDC2s and a recently defined CCR2-dependent CD64-expressing inflammatory cDC2 (inf-cDC2) subset to the draining lymph node compared to antigen alone, while CD26(-)CD64(+)CD88(+) MCs were barely detectable. At 24 h post-vaccination, cDC2s and inf-cDC2s were superior amongst the different subsets in priming antigen-specific CD4(+) T cells, while simultaneously presenting antigen to CD8(+) T cells. Diphtheria toxin (DT) mediated depletion of all DCs prior to vaccination completely abolished adaptive immune responses, while depletion 24 h after vaccination mainly affected CD8(+) T cell responses. Vaccinated mice lacking Flt3 or the chemokine receptor CCR2 showed a marked deficit in inf-cDC2 recruitment and failed to raise proper antibody and T cell responses. Thus, the adjuvant activity of AS01 is associated with the potent activation of subsets of cDC2s, including the newly described inf-cDC2s.
Keywords
MONOPHOSPHORYL-LIPID-A, IN-VIVO DEPLETION, BONE-MARROW, RESPONSES, MONOCYTES, RECEPTOR, MACROPHAGES, ANTIGEN, TRANSPORT, ADULTS, AS01, vaccine, adjuvant, dendritic cell, inf-cDC2, CD64, MAR-1, Fc, receptor

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MLA
Bosteels, Cedric, et al. “CCR2-and Flt3-Dependent Inflammatory Conventional Type 2 Dendritic Cells Are Necessary for the Induction of Adaptive Immunity by the Human Vaccine Adjuvant System AS01.” FRONTIERS IN IMMUNOLOGY, vol. 11, 2021, doi:10.3389/fimmu.2020.606805.
APA
Bosteels, C., Fierens, K., De Prijck, S., Van Moorleghem, J., Vanheerswynghels, M., De Wolf, C., … Lambrecht, B. (2021). CCR2-and Flt3-dependent inflammatory conventional type 2 dendritic cells are necessary for the induction of adaptive immunity by the human vaccine adjuvant system AS01. FRONTIERS IN IMMUNOLOGY, 11. https://doi.org/10.3389/fimmu.2020.606805
Chicago author-date
Bosteels, Cedric, Kaat Fierens, Sofie De Prijck, Justine Van Moorleghem, Manon Vanheerswynghels, Caroline De Wolf, Aurelie Chalon, et al. 2021. “CCR2-and Flt3-Dependent Inflammatory Conventional Type 2 Dendritic Cells Are Necessary for the Induction of Adaptive Immunity by the Human Vaccine Adjuvant System AS01.” FRONTIERS IN IMMUNOLOGY 11. https://doi.org/10.3389/fimmu.2020.606805.
Chicago author-date (all authors)
Bosteels, Cedric, Kaat Fierens, Sofie De Prijck, Justine Van Moorleghem, Manon Vanheerswynghels, Caroline De Wolf, Aurelie Chalon, Catherine Collignon, Hamida Hammad, Arnaud M. Didierlaurent, and Bart Lambrecht. 2021. “CCR2-and Flt3-Dependent Inflammatory Conventional Type 2 Dendritic Cells Are Necessary for the Induction of Adaptive Immunity by the Human Vaccine Adjuvant System AS01.” FRONTIERS IN IMMUNOLOGY 11. doi:10.3389/fimmu.2020.606805.
Vancouver
1.
Bosteels C, Fierens K, De Prijck S, Van Moorleghem J, Vanheerswynghels M, De Wolf C, et al. CCR2-and Flt3-dependent inflammatory conventional type 2 dendritic cells are necessary for the induction of adaptive immunity by the human vaccine adjuvant system AS01. FRONTIERS IN IMMUNOLOGY. 2021;11.
IEEE
[1]
C. Bosteels et al., “CCR2-and Flt3-dependent inflammatory conventional type 2 dendritic cells are necessary for the induction of adaptive immunity by the human vaccine adjuvant system AS01,” FRONTIERS IN IMMUNOLOGY, vol. 11, 2021.
@article{8698092,
  abstract     = {The Adjuvant System AS01 contains monophosphoryl lipid A (MPL) and the saponin QS-21 in a liposomal formulation. AS01 is included in recently developed vaccines against malaria and varicella zoster virus. Like for many other adjuvants, induction of adaptive immunity by AS01 is highly dependent on the ability to recruit and activate dendritic cells (DCs) that migrate to the draining lymph node for T and B cell stimulation. The objective of this study was to more precisely address the contribution of the different conventional (cDC) and monocyte-derived DC (MC) subsets in the orchestration of the adaptive immune response after immunization with AS01 adjuvanted vaccine. The combination of MPL and QS-21 in AS01 induced strong recruitment of CD26(+)XCR1(+) cDC1s, CD26(+)CD172(+) cDC2s and a recently defined CCR2-dependent CD64-expressing inflammatory cDC2 (inf-cDC2) subset to the draining lymph node compared to antigen alone, while CD26(-)CD64(+)CD88(+) MCs were barely detectable. At 24 h post-vaccination, cDC2s and inf-cDC2s were superior amongst the different subsets in priming antigen-specific CD4(+) T cells, while simultaneously presenting antigen to CD8(+) T cells. Diphtheria toxin (DT) mediated depletion of all DCs prior to vaccination completely abolished adaptive immune responses, while depletion 24 h after vaccination mainly affected CD8(+) T cell responses. Vaccinated mice lacking Flt3 or the chemokine receptor CCR2 showed a marked deficit in inf-cDC2 recruitment and failed to raise proper antibody and T cell responses. Thus, the adjuvant activity of AS01 is associated with the potent activation of subsets of cDC2s, including the newly described inf-cDC2s.},
  articleno    = {606805},
  author       = {Bosteels, Cedric and Fierens, Kaat and De Prijck, Sofie and Van Moorleghem, Justine and Vanheerswynghels, Manon and De Wolf, Caroline and Chalon, Aurelie and Collignon, Catherine and Hammad, Hamida and Didierlaurent, Arnaud M. and Lambrecht, Bart},
  issn         = {1664-3224},
  journal      = {FRONTIERS IN IMMUNOLOGY},
  keywords     = {MONOPHOSPHORYL-LIPID-A,IN-VIVO DEPLETION,BONE-MARROW,RESPONSES,MONOCYTES,RECEPTOR,MACROPHAGES,ANTIGEN,TRANSPORT,ADULTS,AS01,vaccine,adjuvant,dendritic cell,inf-cDC2,CD64,MAR-1,Fc,receptor},
  language     = {eng},
  pages        = {12},
  title        = {CCR2-and Flt3-dependent inflammatory conventional type 2 dendritic cells are necessary for the induction of adaptive immunity by the human vaccine adjuvant system AS01},
  url          = {http://dx.doi.org/10.3389/fimmu.2020.606805},
  volume       = {11},
  year         = {2021},
}

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