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HIV1ABTHERAPY SIGNED

Antibody-Mediated Therapy of HIV-1 Infection

Total Cost €

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EC-Contrib. €

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Partnership

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Project "HIV1ABTHERAPY" data sheet

The following table provides information about the project.

Coordinator
KLINIKUM DER UNIVERSITAET ZU KOELN 

Organization address
address: Kerpener Strasse 62
city: KOELN
postcode: 50937
website: www.uk-koeln.de

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Germany [DE]
 Total cost 1˙500˙000 €
 EC max contribution 1˙500˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-STG
 Funding Scheme ERC-STG
 Starting year 2016
 Duration (year-month-day) from 2016-01-01   to  2020-12-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    KLINIKUM DER UNIVERSITAET ZU KOELN DE (KOELN) coordinator 1˙500˙000.00

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 Project objective

Antibodies are destined to neutralize pathogens and can prevent and fight infectious diseases. Over the last years, advances in single B cell cloning resulted in the isolation of highly potent and broad HIV-1 neutralizing antibodies (bNAbs) that have been shown to prevent SHIV infection in non-human primates (NHPs). Recently, we have demonstrated that a combination of bNAbs can suppress HIV-1 replication in humanized mice, reducing viremia to undetectable levels. Moreover, bNAb therapy of SHIV-infected NHPs induced a rapid decline in viremia, followed by a prolonged control due to the long half-life of the antibodies. While these results strongly encourage the clinical evaluation of bNAbs in HIV-1 therapy, it is of critical importance to understand how the therapeutic potential of antibodies can be harnessed in the most effective way. Therefore, we aim to: I.) Identify exceptionally potent HIV-1 neutralizing antibodies that will be a crucial component of immunotherapy. By establishing novel methods for single-cell sorting and high-throughput sequencing we want to identify bNAbs targeting novel epitopes. II.) Prevent HIV-1 escape applying rationally designed treatment strategies targeting conserved functional sites for HIV-1 entry. III.) Evaluate immune markers and function in relation to bNAb administration in humans. Being at the forefront of one of the first clinical trials studying an HIV-1-directed bNAb, we will have the unique opportunity to investigate the interplay of antibody therapy and the host immune system. This proposal aims to strongly advance the field of HIV-1 antibody therapy and therefore enable the introduction of a new therapeutic modality for HIV-1, and will gain insights for antibody-mediated therapy in other infectious diseases.

 Publications

year authors and title journal last update
List of publications.
2016 T. Schoofs, F. Klein, M. Braunschweig, E. F. Kreider, A. Feldmann, L. Nogueira, T. Oliveira, J. C. C. Lorenzi, E. H. Parrish, G. H. Learn, A. P. West, P. J. Bjorkman, S. J. Schlesinger, M. S. Seaman, J. Czartoski, M. J. McElrath, N. Pfeifer, B. H. Hahn, M. Caskey, M. C. Nussenzweig
HIV-1 therapy with monoclonal antibody 3BNC117 elicits host immune responses against HIV-1
published pages: 997-1001, ISSN: 0036-8075, DOI: 10.1126/science.aaf0972
Science 352/6288 2019-06-06
2018 Yotam Bar-On, Henning Gruell, Till Schoofs, Joy A. Pai, Lilian Nogueira, Allison L. Butler, Katrina Millard, Clara Lehmann, Isabelle Suárez, Thiago Y. Oliveira, Theodora Karagounis, Yehuda Z. Cohen, Christoph Wyen, Stefan Scholten, Lisa Handl, Shiraz Belblidia, Juan P. Dizon, Jörg J. Vehreschild, Maggi Witmer-Pack, Irina Shimeliovich, Kanika Jain, Kerstin Fiddike, Kelly E. Seaton, Nicole L. Yates, Jill Horowitz, Roy M. Gulick, Nico Pfeifer, Georgia D. Tomaras, Michael S. Seaman, Gerd Fätkenheuer, Marina Caskey, Florian Klein, Michel C. Nussenzweig
Safety and antiviral activity of combination HIV-1 broadly neutralizing antibodies in viremic individuals
published pages: 1701-1707, ISSN: 1078-8956, DOI: 10.1038/s41591-018-0186-4
Nature Medicine 24/11 2019-06-06
2018 Ching-Lan Lu, Joy A. Pai, Lilian Nogueira, Pilar Mendoza, Henning Gruell, Thiago Y. Oliveira, John Barton, Julio C. C. Lorenzi, Yehuda Z. Cohen, Lillian B. Cohn, Florian Klein, Marina Caskey, Michel C. Nussenzweig, Mila Jankovic
Relationship between intact HIV-1 proviruses in circulating CD4 + T cells and rebound viruses emerging during treatment interruption
published pages: E11341-E11348, ISSN: 0027-8424, DOI: 10.1073/pnas.1813512115
Proceedings of the National Academy of Sciences 115/48 2019-06-06
2019 Marina Caskey, Florian Klein, Michel C. Nussenzweig
Broadly neutralizing anti-HIV-1 monoclonal antibodies in the clinic
published pages: 547-553, ISSN: 1078-8956, DOI: 10.1038/s41591-019-0412-8
Nature Medicine 25/4 2019-06-06
2018 Henning Gruell, Florian Klein
Antibody-mediated prevention and treatment of HIV-1 infection
published pages: , ISSN: 1742-4690, DOI: 10.1186/s12977-018-0455-9
Retrovirology 15/1 2019-06-06
2018 Pilar Mendoza, Henning Gruell, Lilian Nogueira, Joy A. Pai, Allison L. Butler, Katrina Millard, Clara Lehmann, Isabelle Suárez, Thiago Y. Oliveira, Julio C. C. Lorenzi, Yehuda Z. Cohen, Christoph Wyen, Tim Kümmerle, Theodora Karagounis, Ching-Lan Lu, Lisa Handl, Cecilia Unson-O’Brien, Roshni Patel, Carola Ruping, Maike Schlotz, Maggi Witmer-Pack, Irina Shimeliovich, Gisela Kremer, Eleonore Thomas, Kelly E. Seaton, Jill Horowitz, Anthony P. West, Pamela J. Bjorkman, Georgia D. Tomaras, Roy M. Gulick, Nico Pfeifer, Gerd Fätkenheuer, Michael S. Seaman, Florian Klein, Marina Caskey, Michel C. Nussenzweig
Combination therapy with anti-HIV-1 antibodies maintains viral suppression
published pages: 479-484, ISSN: 0028-0836, DOI: 10.1038/s41586-018-0531-2
Nature 561/7724 2019-06-06
2017 Marina Caskey, Till Schoofs, Henning Gruell, Allison Settler, Theodora Karagounis, Edward F Kreider, Ben Murrell, Nico Pfeifer, Lilian Nogueira, Thiago Y Oliveira, Gerald H Learn, Yehuda Z Cohen, Clara Lehmann, Daniel Gillor, Irina Shimeliovich, Cecilia Unson-O\'Brien, Daniela Weiland, Alexander Robles, Tim Kümmerle, Christoph Wyen, Rebeka Levin, Maggi Witmer-Pack, Kemal Eren, Caroline Ignacio, Szilard Kiss, Anthony P West, Hugo Mouquet, Barry S Zingman, Roy M Gulick, Tibor Keler, Pamela J Bjorkman, Michael S Seaman, Beatrice H Hahn, Gerd Fätkenheuer, Sarah J Schlesinger, Michel C Nussenzweig, Florian Klein
Antibody 10-1074 suppresses viremia in HIV-1-infected individuals
published pages: 185-191, ISSN: 1078-8956, DOI: 10.1038/nm.4268
Nature Medicine 23/2 2019-06-06

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