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https://doi.org/10.3390/vaccines9010056
Title: | Liposomal Nanovaccine Containing α-Galactosylceramide and Ganglioside GM3 Stimulates Robust CD8+ T Cell Responses via CD169+ Macrophages and cDC1 | Authors: | Grabowska, Joanna Stolk, Dorian A. Nijen Twilhaar, M.K. Ambrosini, Martino Storm, Gert van der Vliet, Hans J. de Gruijl, Tanja D. Kooyk, Y. den Haan, Joke M. M. |
Keywords: | Alpha galactosylceramide Anti-tumor CD169 macrophage CDC1 Ganglioside GM3 Invariant natural killer T cell Liposomes Vaccination |
Issue Date: | 16-Jan-2021 | Publisher: | MDPI AG | Citation: | Grabowska, Joanna, Stolk, Dorian A., Nijen Twilhaar, M.K., Ambrosini, Martino, Storm, Gert, van der Vliet, Hans J., de Gruijl, Tanja D., Kooyk, Y., den Haan, Joke M. M. (2021-01-16). Liposomal Nanovaccine Containing α-Galactosylceramide and Ganglioside GM3 Stimulates Robust CD8+ T Cell Responses via CD169+ Macrophages and cDC1. Vaccines 9 (1) : 1-19. ScholarBank@NUS Repository. https://doi.org/10.3390/vaccines9010056 | Rights: | Attribution 4.0 International | 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. © 2021 by the authors. Licensee MDPI, Basel, Switzerland. | Source Title: | Vaccines | URI: | https://scholarbank.nus.edu.sg/handle/10635/233798 | ISSN: | 2076-393X | DOI: | 10.3390/vaccines9010056 | Rights: | Attribution 4.0 International |
Appears in Collections: | Elements Staff Publications |
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