Discovery of Self-Assembling Small Molecules as Vaccine Adjuvants.
Angew Chem Int Ed Engl
; 60(2): 961-969, 2021 01 11.
Article
en En
| MEDLINE
| ID: mdl-32979004
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Adyuvantes Inmunológicos
/
Amidas
Límite:
Animals
Idioma:
En
Revista:
Angew Chem Int Ed Engl
Año:
2021
Tipo del documento:
Article
País de afiliación:
Japón
Pais de publicación:
Alemania