Descripción del proyecto
Investigación del mecanismo molecular de los adyuvantes de saponina en las vacunas
Los adyuvantes son componentes esenciales de las vacunas moleculares modernas que aumentan la baja inmunogenicidad de los antígenos y potencian la respuesta inmunitaria. Los mecanismos de acción de muchos adyuvantes de importancia clínica, incluida la saponina QS-21, son poco conocidos. El objetivo principal del proyecto financiado con fondos europeos QS21-Mech es desarrollar nuevas sondas químicas para investigar el mecanismo molecular de los adyuvantes de saponina. Se sintetizarán sondas de fotoafinidad basadas en saponina sintética y a continuación se evaluará su actividad adyuvante en ratones. Las sondas activas de saponina se utilizarán para descubrir los receptores moleculares de estos adyuvantes. Por último, se determinará la identidad del posible receptor mediante análisis proteómicos.
Objetivo
Adjuvants are vital components of modern molecular vaccines that increase the low immunogenicity of subunit peptide and/ or polysaccharide antigens and potentiate the immune response. Despite their key role, the mechanisms of action of many adjuvants, including the clinically-relevant saponin QS-21, are poorly understood, which hampers the rational design of new, improved vaccine adjuvants.
To address this gap and shed light into this fundamental biological mystery, the main goal of this proposal (QS21-Mech) is to develop new chemical probes to investigate the molecular mechanism of saponin adjuvants, one of the most potent and promising class of adjuvants. Using a multidisciplinary approach at the chemistry-biology interface, synthetic saponin-based photoaffinity probes will be chemically synthesized, followed by immunological evaluation for adjuvant activity in mice. The active saponin probes will then be utilized in biological/mechanistic studies to discover the putative molecular receptor of these adjuvants using a chemical proteomics approach. The photoreactive group will be used to cross-link the saponin molecule to the putative interacting partner, while the reporter group will serve as a tag for affinity-purification of the cross-linked adducts. Finally, the identity of the putative receptor will be resolved using MS-based proteomics analysis. The identification of the molecular target of the saponin adjuvants will provide unprecedented mechanistic understanding, facilitating the elucidation of their molecular mechanisms of action, which is of fundamental interest in immunology. This knowledge will enable the rational development of improved saponin adjuvants and optimal adjuvant-antigen combinations for vaccines against a broad range of diseases.
Ámbito científico
Programa(s)
Régimen de financiación
MSCA-IF-EF-ST - Standard EFCoordinador
48160 DERIO VIZCAYA
España