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IMMUNIBY (ERC starting grant)
Third-party funded project
Project title IMMUNIBY (ERC starting grant)
Principal Investigator(s) Pinschewer, Daniel
Organisation / Research unit Departement Biomedizin / Experimental Virology (Pinschewer)
Project start 01.09.2013
Probable end 31.08.2018
Status Completed
Abstract

This project aims for a quantum leap in the understudied area of memory B cell immunity to chronic viral infection. It provides i) a landscape analysis of primary and memory B cell responses to chronic viral challenge, ii) investigates receptor hypermutation of memory B cells for broadened protection against viral escape variants, and iii) studies the role of memory CD4+ T cells in augmenting memory B cell protection in chronic viral infection. Memory B cells represent a main pillar of immunological memory and account for long-term protection by the hepatitis B virus vaccine, the only one to afford protection against a persistent viral infection in humans. Yet our understanding of memory B cell immunity to chronic viral infection remains rudimentary, owing to a lack of advanced methodology and model systems for its investigation. My laboratory has developed a comprehensive set of tools to overcome these hurdles in the prototypic chronic infection model of lymphocytic choriomeningitis virus (LCMV) in mice. We have at hands the first LCMV-neutralizing monoclonal B cell receptor-expressing mouse (unpublished), and will collaborate with a world-leading lab in B cell biology to exploit their novel mouse model for in vivo tracing of polyclonal antigen-specific memory B cells. Combined with genetically engineered LCMV mutants, multi-parameter flow cytometry, state-of-the-art immunological methods, histopathology and deep sequencing of B cell receptor repertoires, these models will allow for unprecedented cell transfer and viral infection studies in vivo. Our leading expertise in LCMV molecular biology and immunology, combined with our partners’ expertise in B cell biology warrants for a high likelihood of success in this ambitious journey to virgin territory. We expect this project to provide a conceptual basis and incentive to successfully exploit memory B cell immunity in the battle against global hepatitis C virus and human immunodeficiency virus pandemics.

Financed by Commission of the European Union

Published results ()

  ID Autor(en) Titel ISSN / ISBN Erschienen in Art der Publikation
3407102  Sommerstein, Rami; Flatz, Lukas; Remy, Melissa M.; Malinge, Pauline; Magistrelli, Giovanni; Fischer, Nicolas; Sahin, Mehmet; Bergthaler, Andreas; Igonet, Sebastien; Ter Meulen, Jan; Rigo, Dorothée; Meda, Paolo; Rabah, Nadia; Coutard, Bruno; Bowden, Thomas A.; Lambert, Paul-Henri; Siegrist, Claire-Anne; Pinschewer, Daniel D.  Arenavirus Glycan Shield Promotes Neutralizing Antibody Evasion and Protracted Infection  1553-7374  PLoS pathogens  Publication: JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift) 
3407104  Darbre, Stephanie; Johnson, Susan; Kallert, Sandra; Lambert, Paul-Henri; Siegrist, Claire-Anne; Pinschewer, Daniel D.  The Nucleoprotein Is Required for Lymphocytic Choriomeningitis Virus-Based Vaccine Vector Immunogenicity  1098-5514  Journal of Virology  Publication: JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift) 
3407106  Penaloza-MacMaster, Pablo; Barber, Daniel L.; Wherry, E. John; Provine, Nicholas M.; Teigler, Jeffrey E.; Parenteau, Lily; Blackmore, Stephen; Borducchi, Erica N.; Larocca, Rafael A.; Yates, Kathleen B.; Shen, Hao; Haining, W. Nicholas; Sommerstein, Rami; Pinschewer, Daniel D.; Ahmed, Rafi; Barouch, Dan H.  Vaccine-elicited CD4 T cells induce immunopathology after chronic LCMV infection  1095-9203  Science  Publication: JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift) 
4407593  Fallet, Benedict; Narr, Kerstin; Ertuna, Yusuf I.; Remy, Melissa; Sommerstein, Rami; Cornille, Karen; Kreutzfeldt, Mario; Page, Nicolas; Zimmer, Gert; Geier, Florian; Straub, Tobias; Pircher, Hanspeter; Larimore, Kevin; Greenberg, Philip D.; Merkler, Doron; Pinschewer, Daniel D.  Interferon-driven Deletion of Antiviral B Cells at the Onset of Chronic Infection  2470-9468  Science Immunology  Publication: JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift) 
4597403  Pinschewer, Daniel D.  Virally vectored vaccine delivery: medical needs, mechanisms, advantages and challenges  1424-7860 ; 1424-3997  Swiss medical weekly  Publication: JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift) 
   

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29/03/2024