Getting the right antibodies from vaccination

Janssen Vaccines & Prevention B.V. (Janssen) and the Leiden University Medical Center (LUMC) combine their expertise to understand the specifics of a protective antibody response to bacterial infection. Janssen develops numerous anti-bacterial vaccines and has a strong background in vaccination models and pre-clinical prediction of efficacy. LUMC contributes its unique ability to perform deep structural characterisation of antibodies and their membrane-bound siblings, the B cell receptors.

Antibiotic resistance threatens the effective treatment of serious bacterial infections. 50% to 90% of current Escherichia coli (E.coli) strains show antibiotic resistance, contributing to a rise in serious and lethal infections. Anti-bacterial vaccines could be an efficient tool to prevent millions of E.coli infections and hundreds of thousands of resulting deaths. However, the efficacy of an anti-bacterial vaccine remains hard to predict.

This project will contribute to a better rational design of anti-bacterial vaccines. Various combinations of vaccines and adjuvants will be tested in preclinical immunisation models. They will purify antibodies and antibody-producing B cells against E.coli and map the qualities of antibody responses that are key to the protection against bacterial infections. These protective responses will be linked to the types of vaccines and adjuvants, which most efficiently trigger them. A focus will be on the promising glycoconjugate vaccines. Importantly, by relying on innovative multi-omics approaches for structural characterisation and integration of functional data from well-established in vitro assays, they will achieve an unprecedented depth and comprehensiveness in the characterisation of antibody responses.

This will allow them to characterise key determinants of the activation of effector functions, such as isotype, subclass and glycosylation, of the antibody response as well as to map the epitopes targeted. Computational integration of the structural data with functional data from bacterial killing and epitope binding will yield a comprehensive understanding of antibody responses in anti-bacterial vaccination.