Antibody-guided design of multivalent nanoparticle vaccines

Vaccines are the most effective single measure to protect populations against infectious diseases without promoting antimicrobial resistance (AMR).

In this proposal, we will harness the rapid developments in protein design and quantitative and structural mass spectrometry to i) enable detailed molecular characterization of circulating serum antibody repertoires directly from clinical samples and ii) establish a generalizable framework for antibody-guided design of next-generation vaccines against bacteria.

The concept relies on identifying and producing protective antigen-specific monoclonal antibodies directly from blood plasma to structurally characterize conserved epitopes in their correct three-dimensional conformation. The structural information of the epitopes is then harnessed to produce multivalent nanoparticle vaccine candidates.

The planned work is focused on the most important members the cholesterol-dependent cytolysins protein family, a family of beta-barrel pore-forming exotoxins.

The fold of this superfamily depends on critical structural hinges that we aim to exploit to construct vaccine candidates that can confer cross pathogen protection.

The work will be novel as it will for the first time, demonstrate the design of a protective vaccine candidate against a protein family associated with distinct bacterial pathogens and infections. The concept will be extendable to other protein families and bacterial pathogens to aid in the combat against AMR.