Potent anti-viral vaccine adjuvant based on pH-degradable nanogels with covalently linked small molecule imidazoquinoline TLR7/8 agonist

Lutz Nuhn; Lien Van Hoecke; Kim Deswarte; Bert Schepens; Yupeng Li; Bart N. Lambrecht; Stefaan De Koker; Sunil A. David; Xavier Saelens; Bruno G. De Geest

doi:10.1016/j.biomaterials.2018.03.026

Potent anti-viral vaccine adjuvant based on pH-degradable nanogels with covalently linked small molecule imidazoquinoline TLR7/8 agonist

Lutz Nuhn, Lien Van Hoecke, Kim Deswarte, Bert Schepens, Yupeng Li, Bart N. Lambrecht, Stefaan De Koker, Sunil A. David, Xavier Saelens, Bruno G. De Geest

Research output: Contribution to journal › Article › peer-review

30 Scopus citations

Abstract

Improving the immunogenicity of subunit vaccines, in particular skewing of the immune response towards Th1 type immunity, is crucial for the development of effective vaccines against intracellular infections and for the development of anti-cancer vaccines. Small molecule TLR7/8 agonist hold high potential for this purpose, but suffer from an undesirable pharmacokinetic profile, resulting in systemic inflammatory responses. An effective solution to this problem is covalent ligation to a larger carrier. Here, a degradable nanogel carrier containing a covalently linked imidazoquinoline (IMDQ) TLR7/8 agonist is explored as adjuvant for vaccination against the respiratory syncytial virus (RSV). In vitro and in vivo experiments in mice provide a solid rational base for preferring nanogels over soluble polymers as IMDQ carrier in terms of cellular uptake and lymph node accumulation.

Original language	English (US)
Pages (from-to)	643-651
Number of pages	9
Journal	Biomaterials
Volume	178
DOIs	https://doi.org/10.1016/j.biomaterials.2018.03.026
State	Published - Sep 2018

Bibliographical note

Funding Information:
B.G.D.G. acknowledges the FWO Flanders and the Flemish Liga Against Cancer for funding. L.N. thanks and the Alexander von Humboldt Foundation for a Feodor Lynen return fellowship and the Fonds der Chemischen Industrie for a Liebig fellowship. LVH is a junior assistant and BS a post-doctoral assistant of the Ghent University department of Biomedical Molecular Biology. S.D. and Y.L. gratefully acknowledge funding from the NIH (NIAID Contract HHSN272201400056C). The authors kindly acknowledge Maria Kokkinopoulou and Ingo Lieberwirth for the transmission electron microscopy images of the nanogels.

Funding Information:
B.G.D.G. acknowledges the FWO Flanders and the Flemish Liga Against Cancer for funding. L.N. thanks and the Alexander von Humboldt Foundation for a Feodor Lynen return fellowship and the Fonds der Chemischen Industrie for a Liebig fellowship. LVH is a junior assistant and BS a post-doctoral assistant of the Ghent University department of Biomedical Molecular Biology. S.D. and Y.L. gratefully acknowledge funding from the NIH (NIAID Contract HHSN272201400056C ). The authors kindly acknowledge Maria Kokkinopoulou and Ingo Lieberwirth for the transmission electron microscopy images of the nanogels.

Publisher Copyright:
© 2018 Elsevier Ltd

Keywords

Lymph nodes
Nanogels
RSV
TLR agonist
Vaccine

UN SDGs

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10.1016/j.biomaterials.2018.03.026

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Potent anti-viral vaccine adjuvant based on pH-degradable nanogels with covalently linked small molecule imidazoquinoline TLR7/8 agonist. / Nuhn, Lutz; Van Hoecke, Lien; Deswarte, Kim; Schepens, Bert; Li, Yupeng; Lambrecht, Bart N.; De Koker, Stefaan; David, Sunil A.; Saelens, Xavier; De Geest, Bruno G.

In: Biomaterials, Vol. 178, 09.2018, p. 643-651.

Research output: Contribution to journal › Article › peer-review

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abstract = "Improving the immunogenicity of subunit vaccines, in particular skewing of the immune response towards Th1 type immunity, is crucial for the development of effective vaccines against intracellular infections and for the development of anti-cancer vaccines. Small molecule TLR7/8 agonist hold high potential for this purpose, but suffer from an undesirable pharmacokinetic profile, resulting in systemic inflammatory responses. An effective solution to this problem is covalent ligation to a larger carrier. Here, a degradable nanogel carrier containing a covalently linked imidazoquinoline (IMDQ) TLR7/8 agonist is explored as adjuvant for vaccination against the respiratory syncytial virus (RSV). In vitro and in vivo experiments in mice provide a solid rational base for preferring nanogels over soluble polymers as IMDQ carrier in terms of cellular uptake and lymph node accumulation.",

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note = "Funding Information: B.G.D.G. acknowledges the FWO Flanders and the Flemish Liga Against Cancer for funding. L.N. thanks and the Alexander von Humboldt Foundation for a Feodor Lynen return fellowship and the Fonds der Chemischen Industrie for a Liebig fellowship. LVH is a junior assistant and BS a post-doctoral assistant of the Ghent University department of Biomedical Molecular Biology. S.D. and Y.L. gratefully acknowledge funding from the NIH (NIAID Contract HHSN272201400056C). The authors kindly acknowledge Maria Kokkinopoulou and Ingo Lieberwirth for the transmission electron microscopy images of the nanogels. Funding Information: B.G.D.G. acknowledges the FWO Flanders and the Flemish Liga Against Cancer for funding. L.N. thanks and the Alexander von Humboldt Foundation for a Feodor Lynen return fellowship and the Fonds der Chemischen Industrie for a Liebig fellowship. LVH is a junior assistant and BS a post-doctoral assistant of the Ghent University department of Biomedical Molecular Biology. S.D. and Y.L. gratefully acknowledge funding from the NIH (NIAID Contract HHSN272201400056C ). The authors kindly acknowledge Maria Kokkinopoulou and Ingo Lieberwirth for the transmission electron microscopy images of the nanogels. Publisher Copyright: {\textcopyright} 2018 Elsevier Ltd",

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AU - Schepens, Bert

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AU - Lambrecht, Bart N.

AU - De Koker, Stefaan

AU - David, Sunil A.

AU - Saelens, Xavier

AU - De Geest, Bruno G.

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Potent anti-viral vaccine adjuvant based on pH-degradable nanogels with covalently linked small molecule imidazoquinoline TLR7/8 agonist

Abstract

Bibliographical note

Keywords

UN SDGs

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