CORDIS - EU research results
CORDIS

Systems-level novel understanding of anti-glycan immunity

Project description

Insight into anti-glycan immunity

High-affinity secretory antibodies (sIgA) have the power to protect from infection and to manipulate gut microbiota composition. However, the design of vaccines that elicit sIgA secretion is limited by the inherently complex biochemistry of bacterial glycans and the need to deliver intact antigen via the highly degradative environment of the intestine. To address these problems, scientists of the EU-funded SNUGly project will generate a toolbox for glycan-binding antibody research to investigate various parameters such as the biophysical properties and the structure of glycan antigens. The project will contribute towards the optimal design of mucosal vaccines and the efficient release of high-affinity anti-glycan sIgA.

Objective

"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
"

Host institution

EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Net EU contribution
€ 1 993 750,00
Address
Raemistrasse 101
8092 Zuerich
Switzerland

See on map

Region
Schweiz/Suisse/Svizzera Zürich Zürich
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 1 993 750,00

Beneficiaries (1)