Discovery of Self-Assembling Small Molecules as Vaccine Adjuvants.
Adjuvants, Immunologic
/ chemistry
Amides
/ chemistry
Animals
Antibodies, Viral
/ blood
Dendritic Cells
/ cytology
Deoxycholic Acid
/ chemistry
Drug Evaluation, Preclinical
Fluorescent Dyes
/ chemistry
Immunity, Innate
Immunoglobulin G
/ blood
Influenza Vaccines
/ chemistry
Interleukin-6
/ metabolism
Macrophages
/ cytology
Mice
Mice, Inbred C57BL
Mice, Knockout
Nanostructures
/ chemistry
RAW 264.7 Cells
Structure-Activity Relationship
Toll-Like Receptor 7
/ metabolism
RNA
chemical biology
nanostructures
self-assembly
viruses
Journal
Angewandte Chemie (International ed. in English)
ISSN: 1521-3773
Titre abrégé: Angew Chem Int Ed Engl
Pays: Germany
ID NLM: 0370543
Informations de publication
Date de publication:
11 01 2021
11 01 2021
Historique:
received:
25
08
2020
pubmed:
27
9
2020
medline:
27
3
2021
entrez:
26
9
2020
Statut:
ppublish
Résumé
Immune potentiators, termed adjuvants, trigger early innate immune responses to ensure the generation of robust and long-lasting adaptive immune responses of vaccines. Presented here is a study that takes advantage of a self-assembling small-molecule library for the development of a novel vaccine adjuvant. Cell-based screening of the library and subsequent structural optimization led to the discovery of a simple, chemically tractable deoxycholate derivative (molecule 6, also named cholicamide) whose well-defined nanoassembly potently elicits innate immune responses in macrophages and dendritic cells. Functional and mechanistic analyses indicate that the virus-like assembly enters the cells and stimulates the innate immune response through Toll-like receptor 7 (TLR7), an endosomal TLR that detects single-stranded viral RNA. As an influenza vaccine adjuvant in mice, molecule 6 was as potent as Alum, a clinically used adjuvant. The studies described here pave the way for a new approach to discovering and designing self-assembling small-molecule adjuvants against pathogens, including emerging viruses.
Identifiants
pubmed: 32979004
doi: 10.1002/anie.202011604
doi:
Substances chimiques
Adjuvants, Immunologic
0
Amides
0
Antibodies, Viral
0
Fluorescent Dyes
0
Immunoglobulin G
0
Influenza Vaccines
0
Interleukin-6
0
Toll-Like Receptor 7
0
Deoxycholic Acid
005990WHZZ
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
961-969Informations de copyright
© 2020 Wiley-VCH GmbH.
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