Liposomal Nanovaccine Containing α-Galactosylceramide and Ganglioside GM3 Stimulates Robust CD8+ T Cell Responses via CD169+ Macrophages and cDC1
Open Access
- 16 January 2021
- Vol. 9 (1), 56
- https://doi.org/10.3390/vaccines9010056
Abstract
Successful anti-cancer vaccines aim to prime and reinvigorate cytotoxic T cells and should therefore comprise a potent antigen and adjuvant. Antigen targeting to splenic CD169+ macrophages was shown to induce robust CD8+ T cell responses via antigen transfer to cDC1. Interestingly, CD169+ macrophages can also activate type I natural killer T-cells (NKT). NKT activation via ligands such as α-galactosylceramide (αGC) serve as natural adjuvants through dendritic cell activation. Here, we incorporated ganglioside GM3 and αGC in ovalbumin (OVA) protein-containing liposomes to achieve both CD169+ targeting and superior DC activation. The systemic delivery of GM3-αGC-OVA liposomes resulted in specific uptake by splenic CD169+ macrophages, stimulated strong IFNγ production by NKT and NK cells and coincided with the maturation of cDC1 and significant IL-12 production. Strikingly, superior induction of OVA-specific CD8+ T cells was detected after immunization with GM3-αGC-OVA liposomes. CD8+ T cell activation, but not B cell activation, was dependent on CD169+ macrophages and cDC1, while activation of NKT and NK cells were partially mediated by cDC1. In summary, GM3-αGC antigen-containing liposomes are a potent vaccination platform that promotes the interaction between different immune cell populations, resulting in strong adaptive immunity and therefore emerge as a promising anti-cancer vaccination strategy.Funding Information
- KWF Kankerbestrijding (VU2014-7200)
- Phospholipid Research Center (VU2016-10449)
This publication has 69 references indexed in Scilit:
- Targeted delivery of lipid antigen to macrophages via the CD169/sialoadhesin endocytic pathway induces robust invariant natural killer T cell activationProceedings of the National Academy of Sciences of the United States of America, 2013
- Safety, Activity, and Immune Correlates of Anti–PD-1 Antibody in CancerThe New England Journal of Medicine, 2012
- The location of splenic NKT cells favours their rapid activation by blood-borne antigenThe EMBO Journal, 2012
- CD169-Positive Macrophages Dominate Antitumor Immunity by Crosspresenting Dead Cell-Associated AntigensImmunity, 2011
- CD169+ macrophages present lipid antigens to mediate early activation of iNKT cells in lymph nodesNature Immunology, 2010
- Effective collaboration between marginal metallophilic macrophages and CD8+dendritic cells in the generation of cytotoxic T cellsProceedings of the National Academy of Sciences of the United States of America, 2009
- CD1d-restricted iNKT cells, the ‘Swiss-Army knife’ of the immune systemCurrent Opinion in Immunology, 2008
- Fine specificity of natural killer T cells against GD3 ganglioside and identification of GM3 as an inhibitory natural killer T‐cell ligandImmunology, 2007
- Differential Antigen Processing by Dendritic Cell Subsets in VivoScience, 2007
- The dominant role of CD8+dendritic cells in cross-presentation is not dictated by antigen captureProceedings of the National Academy of Sciences of the United States of America, 2006