A tractable covalent linker strategy for the production of immunogenic antigen-TLR7/8L bioconjugates
Autor: | S K Lathrop, R Schoener, Casey J. Massena, Jay T. Evans, C J Davison, Hélène G. Bazin, David J. Burkhart |
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Rok vydání: | 2021 |
Předmět: |
Context (language use)
02 engineering and technology Computational biology Catalysis Mice 03 medical and health sciences Adjuvants Immunologic Antigen Materials Chemistry Animals Antigens 030304 developmental biology 0303 health sciences Membrane Glycoproteins Chemistry Immunogenicity Metals and Alloys General Chemistry TLR7 021001 nanoscience & nanotechnology Vaccine efficacy Tlr agonists Surfaces Coatings and Films Electronic Optical and Magnetic Materials Toll-Like Receptor 7 Toll-Like Receptor 8 Covalent bond Ceramics and Composites 0210 nano-technology Linker |
Zdroj: | Chemical Communications. 57:4698-4701 |
ISSN: | 1364-548X 1359-7345 |
DOI: | 10.1039/d1cc00795e |
Popis: | Despite the ease of production and improved safety profiles of recombinant vaccines, the inherently low immunogenicity of unadjuvanted proteins remains an impediment to their widespread adoption. The covalent tethering of TLR agonists to antigenic proteins offers a unique approach to co-deliver both constituents to the same cell-enhancing vaccine efficacy while minimizing reactogenicity. However, the paucity of simple and effective linker chemistries continues to hamper progress. Here, we present a modular, PEG-based linker system compatible with even extremely lipophilic and challenging TLR7/8 agonists. To advance the field and address previous obstacles, we offer the most straightforward and antigen-preserving linker system to date. These antigen-adjuvant conjugates enhance antigen-specific immune responses in mice, demonstrating the power of our approach within the context of modern vaccinology. |
Databáze: | OpenAIRE |
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