Hyaluronic Acid Conjugates of TLR7/8 Agonists for Targeted Delivery to Secondary Lymphoid Tissue
| Autor: | Bart N. Lambrecht, Ans De Beuckelaer, Kim Deswarte, Yupeng Li, Bruno G. De Geest, Euna Yoo, Sunil A. David, Stefan Lienenklaus, Nikunj M. Shukla, Michael J. H. Brush, Kathryn L. Trautman, Alex C. D. Salyer |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Agonist Immunoconjugates medicine.drug_class Biomedical Engineering Pharmaceutical Science Bioengineering Enzyme-Linked Immunosorbent Assay Proof of Concept Study 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Immune system Adjuvants Immunologic In vivo Hyaluronic acid medicine Animals Humans Hyaluronic Acid Receptor Pharmacology Vaccines Membrane Glycoproteins Dose-Response Relationship Drug Chemistry Organic Chemistry 030104 developmental biology Lymphatic system Toll-Like Receptor 7 Toll-Like Receptor 8 030220 oncology & carcinogenesis Cancer research Cytokines Lymph Lymph Nodes Resiquimod Inflammation Mediators Biotechnology |
| Zdroj: | Bioconjugate chemistry. 29(8) |
| ISSN: | 1520-4812 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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