Dissemin is shutting down on January 1st, 2025

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National Academy of Sciences, Proceedings of the National Academy of Sciences, 29(113), p. 8098-8103, 2016

DOI: 10.1073/pnas.1600816113

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pH-degradable imidazoquinoline-ligated nanogels for lymph node-focused immune activation

Journal article published in 2016 by Lutz Nuhn, Nane Vanparijs, Ans De Beuckelaer, Lien Lybaert, Glenn Verstraete ORCID, Kim Deswarte ORCID, Stefan Lienenklaus, Nikunj M. Shukla, Alex C. D. Salyer, Bart N. Lambrecht, Johan Grooten, Sunil A. David, Stefaan De Koker, Bruno G. De Geest
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

Significance The newest generation of small-molecule vaccine adjuvants aims at triggering specific receptors expressed by dendritic cells, the working horses of our immune system. Unfortunately, owing to their small size, upon administration these molecules rapidly enter systemic circulation and cause systemic inflammation. We report on a nanotechnology-based solution for this issue by covalent ligation of a potent immunostimulatory small molecule to hydrogel nanoparticles. This approach allows for lymph node-restricted immune activation and avoids systemic dissemination. Importantly, relative to soluble immunostimulatory compound, nanoparticle ligation yields increased immune activation in the draining lymph nodes and results in strongly increased antibody titers and T-cell responses against an admixed vaccine antigen.