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Antibody-guided design of multivalent nanoparticle vaccines against bacterial pathogens

Project description

Nanoparticle vaccines against bacterial infections

Antimicrobial resistance (AMR) is a significant medical problem that threatens the effectiveness of antibiotics against bacterial infections. Since vaccines prevent infections, they reduce the need for antibiotics and therefore do not promote AMR. Developing new vaccines is thus a powerful strategy to protect populations while addressing the AMR challenge. The ERC-funded NANOBAC project aims to develop nanoparticle vaccines capable of eliciting potent antibody responses. By utilising advances in protein design, researchers will identify protective antibodies from immune individuals, map conserved epitopes and use this knowledge to design multivalent vaccine candidates. The study will use Streptococcus pyogenes as the model pathogen to test these vaccines. Ultimately, the goal is to extend the design to conserved protein epitopes so as to generate cross-pathogen immunity.

Objective

Vaccines are the most effective single measure to protect populations against infectious diseases without promoting antimicrobial resistance (AMR). In this proposal, I intend to harness the rapid developments in protein design and quantitative and structural mass spectrometry to i) enable detailed molecular characterization of circulating serum antibody repertories, ii) establish a generalizable framework for antibody-guided design of next-generation nanoparticle vaccines against bacteria and iii) use the developed nanoparticle vaccines to investigate structural properties of protective antibody responses required for immunity.

The planned work relies on identifying and producing protective antigen-specific monoclonal antibodies from immune individuals. These antibodies are used to structurally characterize conserved epitopes in their correct three-dimensional conformation. The structural information is then harnessed to design multivalent nanoparticle vaccine candidates. The planned work is focused on i) determining the optimal combination of epitopes that generates the highest level of protection using Streptococcus pyogenes as a model system, ii) determine the molecular properties of the circulating serum antibody response that mediates the protection and iii) modify the epitope design to target conserved structural motifs typically found within protein families to produce immunogens that 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.

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2024-ADG

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Host institution

LUNDS UNIVERSITET
Net EU contribution

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€ 2 485 312,00
Address
Paradisgatan 5c
22100 Lund
Sweden

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Region
Södra Sverige Sydsverige Skåne län
Activity type
Higher or Secondary Education Establishments
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Total cost

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