Liposomal Nanovaccine Containing α-Galactosylceramide and Ganglioside GM3 Stimulates Robust CD8+ T Cell Responses via CD169+ Macrophages and cDC1

Grabowska, Joanna; Stolk, Dorian A.; Nijen Twilhaar, Maarten K.; Ambrosini, Martino; Storm, Gert; van der Vliet, Hans J.; de Gruijl, Tanja D.; van Kooyk, Yvette; den Haan, Joke M.M.

doi:10.3390/vaccines9010056

Open AccessArticle

Liposomal Nanovaccine Containing α-Galactosylceramide and Ganglioside GM3 Stimulates Robust CD8⁺ T Cell Responses via CD169⁺ Macrophages and cDC1

by

Joanna Grabowska

^1,†,

Dorian A. Stolk

^1,†

,

Maarten K. Nijen Twilhaar

¹,

Martino Ambrosini

¹,

Gert Storm

^2,3,4,

Hans J. van der Vliet

^5,6,

Tanja D. de Gruijl

⁵,

Yvette van Kooyk

¹ and

Joke M.M. den Haan

^1,*

¹

Department of Molecular Cell Biology and Immunology, Amsterdam UMC, Cancer Center Amsterdam, Amsterdam Infection and Immunity Institute, Vrije Universiteit Amsterdam, 1081 HZ Amsterdam, The Netherlands

²

Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands

³

Department of Biomaterials Science and Technology, University of Twente, 7500 AE Enschede, The Netherlands

⁴

Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore

⁵

Department of Medical Oncology, Amsterdam UMC, Cancer Center Amsterdam, Amsterdam Infection and Immunity Institute, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands

⁶

Lava Therapeutics, 3584 CM Utrecht, The Netherlands

^*

Author to whom correspondence should be addressed.

^†

Authors contributed equally.

Vaccines 2021, 9(1), 56; https://doi.org/10.3390/vaccines9010056

Submission received: 16 December 2020 / Revised: 5 January 2021 / Accepted: 10 January 2021 / Published: 16 January 2021

(This article belongs to the Special Issue Dendritic Cell Immunotherapies: An Opportunity in the Fight against Cancer and Beyond)

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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.

Keywords: vaccination; liposomes; anti-tumor; CD169 macrophage; cDC1; invariant natural killer T cell; alpha galactosylceramide; ganglioside GM3

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MDPI and ACS Style

Grabowska, J.; Stolk, D.A.; Nijen Twilhaar, M.K.; Ambrosini, M.; Storm, G.; van der Vliet, H.J.; de Gruijl, T.D.; van Kooyk, Y.; den Haan, J.M.M. Liposomal Nanovaccine Containing α-Galactosylceramide and Ganglioside GM3 Stimulates Robust CD8⁺ T Cell Responses via CD169⁺ Macrophages and cDC1. Vaccines 2021, 9, 56. https://doi.org/10.3390/vaccines9010056

AMA Style

Grabowska J, Stolk DA, Nijen Twilhaar MK, Ambrosini M, Storm G, van der Vliet HJ, de Gruijl TD, van Kooyk Y, den Haan JMM. Liposomal Nanovaccine Containing α-Galactosylceramide and Ganglioside GM3 Stimulates Robust CD8⁺ T Cell Responses via CD169⁺ Macrophages and cDC1. Vaccines. 2021; 9(1):56. https://doi.org/10.3390/vaccines9010056

Chicago/Turabian Style

Grabowska, Joanna, Dorian A. Stolk, Maarten K. Nijen Twilhaar, Martino Ambrosini, Gert Storm, Hans J. van der Vliet, Tanja D. de Gruijl, Yvette van Kooyk, and Joke M.M. den Haan. 2021. "Liposomal Nanovaccine Containing α-Galactosylceramide and Ganglioside GM3 Stimulates Robust CD8⁺ T Cell Responses via CD169⁺ Macrophages and cDC1" Vaccines 9, no. 1: 56. https://doi.org/10.3390/vaccines9010056

APA Style

Grabowska, J., Stolk, D. A., Nijen Twilhaar, M. K., Ambrosini, M., Storm, G., van der Vliet, H. J., de Gruijl, T. D., van Kooyk, Y., & den Haan, J. M. M. (2021). Liposomal Nanovaccine Containing α-Galactosylceramide and Ganglioside GM3 Stimulates Robust CD8⁺ T Cell Responses via CD169⁺ Macrophages and cDC1. Vaccines, 9(1), 56. https://doi.org/10.3390/vaccines9010056

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Liposomal Nanovaccine Containing α-Galactosylceramide and Ganglioside GM3 Stimulates Robust CD8⁺ T Cell Responses via CD169⁺ Macrophages and cDC1

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