SNUGly
Financiado
Systems level novel understanding of anti glycan immunity
"Intestinal bacteria have an enormous influence on health, both in the form of major pathogens and as major constituents of the microbiota. We have demonstrated that high-affinity secretory antibodies (sIgA) offer huge potential t...
"Intestinal bacteria have an enormous influence on health, both in the form of major pathogens and as major constituents of the microbiota. We have demonstrated that high-affinity secretory antibodies (sIgA) offer huge potential to protect from infection and to manipulate microbiota composition. However, designing good oral vaccines to induce high-affinity sIgA is a compound problem. Most protective anti-bacterial sIgA targets bacterial glycans, requiring an understanding of inherently difficult glycan biochemistry. We also need to deliver intact antigen via the highly degradative environment of the intestine. Whole-cell inactivated oral vaccines can induce high-affinity sIgA against some glycan structures, but we have an incomplete picture of what determines the success/failure of these vaccines. By combining advanced biophysical methods (e.g. atomic force spectroscopy), fluorescence and electron microscopy, and synthetic biology, we aim to remove this mystery. Our objectives are:
1) Generate a ""toolbox"" for glycan-binding antibody research: Recombinant antibodies, BCR knock-in mice and defined glycan antigens as purified molecules, on whole bacteria or on virus-like particle will be developed for model antigens: Salmonella Typhimurium O-antigen and the E.coli K100 capsule.
2) Determine the quantitative relationship between glycan antigen sampling into gut-associated lymphoid tissues and particle size, glycan flexibility/structure, digestion resistance and natural IgA binding.
3) Determine how biophysical properties of glycan antigens affect B cell antigen uptake, T cell help and antibody affinity maturation.
4) Combine models of antigen sampling efficiency and anti-glycan antibody affinity maturation to generate a systems-level model of mucosal vaccine efficacy.
This will uncover the fundamental principles governing the induction of high-affinity anti-glycan sIgA, driving urgently required progress in mucosal vaccine design
"
ver más
Duración del proyecto: 62 meses
Fecha Inicio: 2020-04-28
Fecha Fin: 2025-06-30
Fecha Fin: 2025-06-30
Línea de financiación: concedida
El organismo H2020 notifico la concesión del proyecto el día 2020-04-28
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
ERC-2019-COG:
ERC Consolidator Grant
Cerrada
hace 5 años
Presupuesto
El presupuesto total del proyecto asciende a
2M€
Líder del proyecto
EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
No se ha especificado una descripción o un objeto social para esta compañía.
828.63K€ |
Participante