BROADimmune SIGNED
Structural, genetic and functional analyses of broadly neutralizing antibodies against human pathogens
Total Cost €
0EC-Contrib. €
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Project "BROADimmune" data sheet
The following table provides information about the project.
| Coordinator |
FONDAZIONE PER L ISTITUTO DI RICERCA IN BIOMEDICINA
Organization address contact info |
| Coordinator Country | Switzerland [CH] |
| Project website | https://www.irb.usi.ch/structural-genetic-and-functional-analyses-broadly-neutralizing-antibodies-against-human-pathogens |
| Total cost | 1˙867˙500 € |
| EC max contribution | 1˙867˙500 € (100%) |
| Programme |
1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC)) |
| Code Call | ERC-2014-ADG |
| Funding Scheme | ERC-ADG |
| Starting year | 2015 |
| Duration (year-month-day) | from 2015-10-01 to 2020-09-30 |
Partnership
Take a look of project's partnership.
| # | ||||
|---|---|---|---|---|
| 1 | FONDAZIONE PER L ISTITUTO DI RICERCA IN BIOMEDICINA | CH (BELLINZONA) | coordinator | 1˙867˙500.00 |
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Project objective
The overall goal of this project is to understand the molecular mechanisms that lead to the generation of potent and broadly neutralizing antibodies against medically relevant pathogens, and to identify the factors that limit their production in response to infection or vaccination with current vaccines. We will use high-throughput cellular screens to isolate from immune donors clonally related antibodies to different sites of influenza hemagglutinin, which will be fully characterized and sequenced in order to reconstruct their developmental pathways. Using this approach, we will ask fundamental questions with regards to the role of somatic mutations in affinity maturation and intraclonal diversification, which in some cases may lead to the generation of autoantibodies. We will combine crystallography and long time-scale molecular dynamics simulation to understand how mutations can increase affinity and broaden antibody specificity. By mapping the B and T cell response to all sites and conformations of influenza hemagglutinin, we will uncover the factors, such as insufficient T cell help or the instability of the pre-fusion hemagglutinin, that may limit the generation of broadly neutralizing antibodies. We will also perform a broad analysis of the antibody response to erythrocytes infected by P. falciparum to identify conserved epitopes on the parasite and to unravel the role of an enigmatic V gene that appears to be involved in response to blood-stage parasites. The hypotheses tested are strongly supported by preliminary observations from our own laboratory. While these studies will contribute to our understanding of B cell biology, the results obtained will also have translational implications for the development of potent and broad-spectrum antibodies, for the definition of correlates of protection, and for improving vaccine design.
Publications
| year | authors and title | journal | last update |
|---|---|---|---|
| 2016 |
Antonio Lanzavecchia, Alexander Frühwirth, Laurent Perez, Davide Corti Antibody-guided vaccine design: identification of protective epitopes published pages: 62-67, ISSN: 0952-7915, DOI: 10.1016/j.coi.2016.06.001 |
Current Opinion in Immunology 41 | 2019-08-30 |
| 2018 |
Joshua Tan, Brandon K Sack, David Oyen, Isabelle Zenklusen, Luca Piccoli, Sonia Barbieri, Mathilde Foglierini, Chiara Silacci Fregni, Jessica Marcandalli, Said Jongo, Salim Abdulla, Laurent Perez, Giampietro Corradin, Luca Varani, Federica Sallusto, Betty Kim Lee Sim, Stephen L Hoffman, Stefan H I Kappe, Claudia Daubenberger, Ian A Wilson, Antonio Lanzavecchia A public antibody lineage that potently inhibits malaria infection through dual binding to the circumsporozoite protein published pages: 401-407, ISSN: 1078-8956, DOI: 10.1038/nm.4513 |
Nature Medicine 24/4 | 2019-08-30 |
| 2017 |
Kathrin Pieper, Joshua Tan, Luca Piccoli, Mathilde Foglierini, Sonia Barbieri, Yiwei Chen, Chiara Silacci-Fregni, Tobias Wolf, David Jarrossay, Marica Anderle, Abdirahman Abdi, Francis M. Ndungu, Ogobara K. Doumbo, Boubacar Traore, Tuan M. Tran, Said Jongo, Isabelle Zenklusen, Peter D. Crompton, Claudia Daubenberger, Peter C. Bull, Federica Sallusto, Antonio Lanzavecchia Public antibodies to malaria antigens generated by two LAIR1 insertion modalities published pages: 597-601, ISSN: 0028-0836, DOI: 10.1038/nature23670 |
Nature 548/7669 | 2019-08-30 |
| 2018 |
Antonio Lanzavecchia Dissecting human antibody responses: useful, basic and surprising findings published pages: e8879, ISSN: 1757-4676, DOI: 10.15252/emmm.201808879 |
EMBO Molecular Medicine 10/3 | 2019-08-30 |
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