New Synthetic Saponin Adjuvants and Self-Adjuvanting Conjugate Vaccines
- Autores: Roberto Fuentes García
- Directores de la Tesis: Alberto Fernández Tejada (dir. tes.), María Nuria Sotomayor Anduiza (tut. tes.)
- Lectura: En la Universidad del País Vasco - Euskal Herriko Unibertsitatea ( España ) en 2025
- Idioma: inglés
- Programa de doctorado: Programa de Doctorado en Química Sintética e Industrial por la Universidad del País Vasco/Euskal Herriko Unibertsitatea y la Universidad Pública de Navarra
- Materias:
- Enlaces
- Tesis en acceso abierto en: ADDI
- Resumen
The research presented in this Ph.D. thesis addresses the synthesis of novel QS-21-based saponins and their multidisciplinary evaluation, providing fundamental insights into structure-activity relationships (SAR). As one of the most promising carbohydrate-based adjuvants, QS-21 has demonstrated unique potency in boosting immune responses. Challenges such as scarcity, structural complexity, and hydrolytic instability of the natural source have been overcome over the past decade, leading to the development of simplified synthetic lead saponins.
Continuing through the application of synthetic organic chemistry, more specifically, carbohydrate chemistry, these lead saponins have been further improved. The exploration of streamlined synthetic approaches using commercially available carbohydrates has validated the identity of the linear oligosaccharide domain through immunological and computational studies. Moreover, modifications of the triterpene domain, originally considered stationary and unmodifiable, have paved the way for enhanced activity, leading to a new generation of QS-21-based synthetic saponins. Beyond this, these modifications of the triterpene domain, combined with the well-established conjugatable amino acyl chain, has enabled the development of novel antigen-conjugated adjuvants, paving the way for future applications in cancer immunotherapy with self-adjuvanting vaccines.
