Project description
Safe and affordable antivenoms on the horizon
Venomous snakebites affect 2.5 million and kill around 100 000 people each year. Conventional antivenoms often cause severe side effects and anaphylaxis in patients and are costly to manufacture. The EU-funded MABSTER project will develop a cost-effective approach to identify and engineer human monoclonal antibodies with special toxin-binding properties making them sensitive to regulation by the microenvironment (e.g. pH). Project research will harness phage display selection, high-density peptide microarray technology, and antibody engineering methods to discover and develop human monoclonal antibodies that are broadly cross-reactive, enabling them to neutralise several different venom toxins at the same time. Successful outcome of the project might generate new ways to design biotherapeutics for other complex indications, such as cancer as well as infectious and parasitic diseases.
Objective
Snakebite envenoming is a Neglected Tropical Disease (NTD) that each year affects 2.5 million victims and kills >100,000, unless they are treated with antivenom. Conventional antivenoms, derived from immunized animals, inflict serum sickness and anaphylaxis in patients, and are costly to manufacture. Monoclonal human antibodies with special toxin-binding properties that are sensitive towards regulation by their microenvironment (e.g. pH), which may be discovered using phage display selection, may solve this issue, providing significant societal impact by enabling the development of cost-effective antivenoms to victims in low and middle-income countries. In this project, phage display selection, high-density peptide microarray technology, and antibody engineering techniques will in three scientific objectives be harnessed in the pursuit of developing novel methodologies for discovery of therapeutic human monoclonal antibodies that are recyclable (can neutralize more than one snake toxin per antibody), broadly cross-reactive (can neutralize different types of snake toxins), and that are both broadly cross-reactive and recyclable at the same time. This will open up for entirely new ways of designing biotherapeutics against complex indications, such snakebite envenoming, but also cancer, infectious, and parasitic diseases, where the targets can be elusive due to hyper-mutability. The ERC Starting Grant offers a unique opportunity to consolidate me as an international key scientific researcher in this field of antibody discovery and NTDs. I have already independently led a research group in this area for 2 years, I have in-depth experience with toxin-targeted antibody discovery (my dr.tech dissertation similar to the German “habilitation” will be submitted during fall 2018), and I am already involved in high level policy in the field of snakebite envenoming via my role as a scientific advisor for the World Health Organization.
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Funding Scheme
ERC-STG - Starting GrantHost institution
2800 Kongens Lyngby
Denmark