Hyaluronic Acid Conjugates of TLR7/8 Agonists for Targeted Delivery to Secondary Lymphoid Tissue

Euna Yoo, Alex C.D. Salyer, Michael J.H. Brush, Yupeng Li, Kathryn L. Trautman, Nikunj M. Shukla, Ans De Beuckelaer, Stefan Lienenklaus, Kim Deswarte, Bart N. Lambrecht, Bruno G. De Geest, Sunil A. David

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


Immunogens carried in lymphatic fluid drain via afferent vessels into regional lymph nodes and facilitate the efficient induction of appropriate immune responses. The lymphatic system possesses receptors recognizing hyaluronic acid (HA). Covalent conjugates of small-molecule TLR7/8 agonists with HA are entirely devoid of immunostimulatory activity in vitro. In murine models of immunization, however, such conjugates traffic to lymph nodes, where they are "unmasked", releasing the small molecule TLR7/8 agonist from the carrier polysaccharide. The resulting focal immunostimulation is manifested in potent adjuvantic effects with negligible systemic exposure. The efficient delivery of immunogens has been a major challenge in the development of subunit vaccines, and enhancing targeted delivery of immunogens to secondary lymphoid organs might be a promising approach for improving vaccine efficacy, as well as safety.

Original languageEnglish (US)
Pages (from-to)2741-2754
Number of pages14
JournalBioconjugate Chemistry
Issue number8
StatePublished - Aug 15 2018

Bibliographical note

Funding Information:
This work was supported by NIH/NIAID Contract No. HHSN272201400056C. B.G.D.G. acknowledges the Flanders Research Fund, Ghent Univ., (BOF-GOA) and the Flemish League against Cancer for funding.

Publisher Copyright:
© 2018 American Chemical Society.


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