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- Title
Diversification of a Novel α‐Galactosyl Ceramide Hotspot Boosts the Adjuvant Properties in Parenteral and Mucosal Vaccines.
- Authors
Méndez, Yanira; Vasco, Aldrin V.; Ebensen, Thomas; Schulze, Kai; Yousefi, Mohammad; Davari, Mehdi D.; Wessjohann, Ludger A.; Guzmán, Carlos A.; Rivera, Daniel G.; Westermann, Bernhard
- Abstract
The development of potent adjuvants is an important step for improving the performance of subunit vaccines. CD1d agonists, such as the prototypical α‐galactosyl ceramide (α‐GalCer), are of special interest due to their ability to activate iNKT cells and trigger rapid dendritic cell maturation and B‐cell activation. Herein, we introduce a novel derivatization hotspot at the α‐GalCer skeleton, namely the N‐substituent at the amide bond. The multicomponent diversification of this previously unexplored glycolipid chemotype space permitted the introduction of a variety of extra functionalities that can either potentiate the adjuvant properties or serve as handles for further conjugation to antigens toward the development of self‐adjuvanting vaccines. This strategy led to the discovery of compounds eliciting enhanced antigen‐specific T cell stimulation and a higher antibody response when delivered by either the parenteral or the mucosal route, as compared to a known potent CD1d agonist. Notably, various functionalized α‐GalCer analogues showed a more potent adjuvant effect after intranasal immunization than a PEGylated α‐GalCer analogue previously optimized for this purpose. Ultimately, this work could open multiple avenues of opportunity for the use of mucosal vaccines against microbial infections.
- Subjects
CERAMIDES; T cells; B cells; VACCINES; VACCINE development; ANTIBODY formation; DENDRITIC cells
- Publication
Angewandte Chemie, 2024, Vol 136, Issue 1, p1
- ISSN
0044-8249
- Publication type
Academic Journal
- DOI
10.1002/ange.202310983