Project description
Probing into the molecular mechanism of saponin vaccine adjuvants
Adjuvants are essential components of modern molecular vaccines that increase the low immunogenicity of antigens and potentiate the immune response. The mechanisms of action of many clinically relevant adjuvants, including saponin QS-21, are poorly understood. The main goal of the EU-funded QS21-Mech project is to develop new chemical probes to investigate the molecular mechanism of saponin adjuvants. Synthetic saponin-based photoaffinity probes will be synthesised, followed by the evaluation of their adjuvant activity in mice. The active saponin probes will be utilised to discover the molecular receptors of these adjuvants. Finally, the identity of the putative receptor will be resolved using proteomics analysis.
Objective
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.
Fields of science
Programme(s)
Funding Scheme
MSCA-IF-EF-ST - Standard EFCoordinator
48160 DERIO VIZCAYA
Spain