How antibodies and complement orchestrate protective immune responses against bacteria

Project Information

ACCENT

Grant agreement ID: 101001937

DOI

10.3030/101001937

EC signature date 16 February 2021

Start date 1 January 2022

End date 31 December 2026

Funded under

• EXCELLENT SCIENCE - European Research Council (ERC)

Total cost

€ 2 000 000,00

EU contribution

€ 2 000 000,00

Coordinated by

UNIVERSITAIR MEDISCH CENTRUM UTRECHT
Netherlands

Periodic Reporting for period 2 - ACCENT (How antibodies and complement orchestrate protective immune responses against bacteria)

Reporting period: 2023-07-01 to 2024-12-31

Summary of the context and overall objectives of the project

Due to antibiotic resistance, there is now great interest in the development of alternative therapies against bacterial infections.
One way to achieve this is to develop antibodies that can boost the host immune system and help vulnerable patients to clear the infection.

With this ERC grant, I want to generate a better understanding of how antibodies protect ourselves against infection. When a person develops an infection, the body makes all kinds of different antibodies. Some antibodies can kill the bacteria. They do this by activating the "complement system"; this is a network of proteins in the blood that can ‘drill’ holes (pores) in the cell membrane of bacteria. We don't yet understand why some antibodies can kill bacteria well whereas others cannot.
If you understand that process, you can very quickly translate it into the development of antibody therapies (and perhaps vaccines).

We will be focusing the research on E. coli bacterium, because it is responsible for many antibiotic-resistant infections.
The overall objectives are to identify human antibodies against E. coli bacteria and use them to find out in detail how antibodies activate the complement system and combat the bacteria. Altogether, this grant will lead to fundamental knowledge about the functioning of the immune system and provide a biological basis for the development of antibody-based therapies against bacteria.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

We successfully developed methods to isolate antibodies against E. coli from human blood and study their functionality.
We discovered several ways to improve the killing of bacteria via antibodies.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

Progress beyond state of the art:
Our results on how antibodies can be improved will impact antibody developments in other fields such as cancer and autoimmunity.

Expected results:
1) novel antibodies driving complement-dependent killing of E. coli
2) basic principles by which antibodies induce complement activation and bacterial killing via MAC and neutrophils
3) understanding functional antibody responses during infections

Antibodies that bind bacterial cells can kill bacteria via complement pores