Center for Molecular Medicine Cologne
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Klein, Florian - assoc. RG 10

Antibody-mediated therapy and prevention of infectious pathogens

Introduction

Our Laboratory focuses on human immunology with a strong interest in the development of B lymphocytes and antibodies.

In particular, we are interested in the antibody response to HIV-1 and other infectious pathogens.

Our Aims

We aim to precisely understand the biology of humoral immunity and to use this knowledge to effectively prevent and treat infectious diseases.

To this end, our laboratory works with a wide range of techniques in molecular immunology and conducts clinical trials that enable us to translate our findings into clinical applications.

Our group is dedicated to provide an excellent work environment to train young scientists and for pursuing forefront and innovative research.

  1. Akkina R, Allam A, Balazs AB, Blankson JN, Burnett JC, Casares S, Garcia JV, Hasenkrug KJ, Kashanchi F, Kitchen SG, Klein F, Kumar P, Luster AD, Poluektova LY, Rao M, Sanders-Beer BE, Shultz LD, and Zack JA (2016). Improvements and limitations of humanized mouse models for hiv research: Nih/niaid "meet the experts" 2015 workshop summary. AIDS Res Hum Retroviruses 32, 109-119.
  2. Gautam R, Nishimura Y, Pegu A, Nason MC, Klein F, Gazumyan A, Golijanin J, Buckler-White A, Sadjadpour R, Wang K, Mankoff Z, Schmidt SD, Lifson JD, Mascola JR, Nussenzweig MC, and Martin MA (2016). A single injection of anti-hiv-1 antibodies protects against repeated shiv challenges. Nature 533, 105-109.
  3. Schoofs T, Klein F, Braunschweig M, Kreider EF, Feldmann A, Nogueira L, Oliveira T, Lorenzi JC, Parrish EH, Learn GH, West AP, Jr., Bjorkman PJ, Schlesinger SJ, Seaman MS, Czartoski J, McElrath MJ, Pfeifer N, Hahn BH, Caskey M, and Nussenzweig MC (2016). Hiv-1 therapy with monoclonal antibody 3bnc117 elicits host immune responses against hiv-1. Science 352, 997-1001.
  4. Caskey, M.*, Klein, F.*, Lorenzi, J.C., Seaman, M.S., West, A.P., Jr., Buckley, N., Kremer, G., Nogueira, L., Braunschweig, M., Scheid, J.F., Horwitz, J.A., Shimeliovich, I., Ben-Avraham, S., Witmer-Pack, M., Platten, M., Lehmann, C., Burke, L.A., Hawthorne, T., Gorelick, R.J., Walker, B.D., Keler, T., Gulick, R.M., Fatkenheuer, G., Schlesinger, S.J., and Nussenzweig, M.C., Viraemia suppressed in HIV-1-infected humans by broadly neutralizing antibody 3BNC117.Nature (2015).
  5.  Klein, F., Nogueira, L., Nishimura, Y., Phad, G., West, A.P., Jr., Halper-Stromberg, A., Horwitz, J.A., Gazumyan, A., Liu, C., Eisenreich, T.R., Lehmann, C., Fatkenheuer, G., Williams, C., Shingai, M., Martin, M.A., Bjorkman, P.J., Seaman, M.S., Zolla-Pazner, S., Karlsson Hedestam, G.B., and Nussenzweig, M.C., Enhanced HIV-1 immunotherapy by commonly arising antibodies that target virus escape variants.J Exp Med.(2014).
  6. Klein, F., Mouquet, H., Dosenovic, P., Scheid, J.F., Scharf, L., and Nussenzweig, M.C., Antibodies in HIV-1 vaccine development and therapy. Science (2013).
  7. Klein, F., Diskin, R., Scheid, J.F., Gaebler, C., Mouquet, H., Georgiev, I.S., Pancera, M., Zhou, T., Incesu, R.B., Fu, B.Z., Gnanapragasam, P.N., Oliveira, T.Y., Seaman, M.S., Kwong, P.D., Bjorkman, P.J., and Nussenzweig, M.C., Somatic mutations of the immunoglobulin framework are generally required for broad and potent HIV-1 neutralization. Cell (2013).
  8. Klein, F., Halper-Stromberg, A., Horwitz, J.A., Gruell, H., Scheid, J.F., Bournazos, S., Mouquet, H., Spatz, L.A., Diskin, R., Abadir, A., Zang, T., Dorner, M., Billerbeck, E., Labitt, R.N., Gaebler, C., Marcovecchio, P.M., Incesu, R.B., Eisenreich, T.R., Bieniasz, P.D., Seaman, M.S., Bjorkman, P.J., Ravetch, J.V., Ploss, A., and Nussenzweig, M.C., HIV therapy by a combination of broadly neutralizing antibodies in humanized mice. Nature (2012).
  • Augustin M, Horn C, Ercanoglu MS, Sandaradura de Silva U, Bondet V, Suarez I, Chon SH, Nierhoff D, Knops E, Heger E, Vivaldi C, Schafer H, Oette M, Fatkenheuer G, Klein F, Duffy D, Muller-Trutwin M, and Lehmann C (2022). CXCR3 Expression Pattern on CD4+ T Cells and IP-10 Levels with Regard to the HIV-1 Reservoir in the Gut-Associated Lymphatic Tissue. Pathogens11. doi:10.3390/pathogens11040483.
  • Dewald F, Suarez I, Johnen R, Grossbach J, Moran-Tovar R, Steger G, Joachim A, Rubio GH, Fries M, Behr F, Kley J, Lingnau A, Kretschmer A, Gude C, Baeza-Flores G, Del Valle DL, Roblero-Hernandez A, Magana-Cerino J, Hernandez AT, Ruiz-Quinones J, Schega K, Linne V, Junker L, Wunsch M, Heger E, Knops E, Di Cristanziano V, Meyer M, Hunseler C, Weber LT, Luers JC, Quade G, Wisplinghoff H, Tiemann C, Zotz R, Jomaa H, Pranada A, Herzum I, Cullen P, Schmitz FJ, Philipsen P, Kirchner G, Knabbe C, Hellmich M, Buess M, Wolff A, Kossow A, Niessen J, Jeworutzki S, Schrapler JP, Lassig M, Dotsch J, Fatkenheuer G, Kaiser R, Beyer A, Rybniker J, and Klein F (2022). Effective high-throughput RT-qPCR screening for SARS-CoV-2 infections in children. Nat Commun13, 3640. doi:10.1038/s41467-022-30664-2.
  • Ercanoglu MS, Gieselmann L, Dahling S, Poopalasingam N, Detmer S, Koch M, Korenkov M, Halwe S, Kluver M, Di Cristanziano V, Janicki H, Schlotz M, Worczinski J, Gathof B, Gruell H, Zehner M, Becker S, Vanshylla K, Kreer C, and Klein F (2022). No substantial preexisting B cell immunity against SARS-CoV-2 in healthy adults. iScience25, 103951. doi:10.1016/j.isci.2022.103951.
  • Poopalasingam N, Korenkov M, Ashurov A, Strobel J, Fish I, Hellmich M, Gruell H, Lehmann C, Heger E, and Klein F (2022). Determining the reliability of rapid SARS-CoV-2 antigen detection in fully vaccinated individuals. J Clin Virol148, 105119. doi:10.1016/j.jcv.2022.105119.
  • Schweitzer F, Goereci Y, Franke C, Silling S, Bosl F, Maier F, Heger E, Deiman B, Pruss H, Onur OA, Klein F, Fink GR, Di Cristanziano V, and Warnke C (2022). Cerebrospinal Fluid Analysis Post-COVID-19 Is Not Suggestive of Persistent Central Nervous System Infection. Ann Neurol91, 150-157. doi:10.1002/ana.26262.
  • Vanshylla K, Fan C, Wunsch M, Poopalasingam N, Meijers M, Kreer C, Kleipass F, Ruchnewitz D, Ercanoglu MS, Gruell H, Munn F, Pohl K, Janicki H, Nolden T, Bartl S, Stein SC, Augustin M, Dewald F, Gieselmann L, Schommers P, Schulz TF, Sander LE, Koch M, Luksza M, Lassig M, Bjorkman PJ, and Klein F (2022). Discovery of ultrapotent broadly neutralizing antibodies from SARS-CoV-2 elite neutralizers. Cell Host Microbe30, 69-82 e10. doi:10.1016/j.chom.2021.12.010.
  • Weber T, Potthoff J, Bizu S, Labuhn M, Dold L, Schoofs T, Horning M, Ercanoglu MS, Kreer C, Gieselmann L, Vanshylla K, Langhans B, Janicki H, Stroh LJ, Knops E, Nierhoff D, Spengler U, Kaiser R, Bjorkman PJ, Krey T, Bankwitz D, Pfeifer N, Pietschmann T, Flyak AI, and Klein F (2022). Analysis of antibodies from HCV elite neutralizers identifies genetic determinants of broad neutralization. Immunity55, 341-354 e347. doi:10.1016/j.immuni.2021.12.003.
  • Gruell H, Vanshylla K, Weber T, Barnes CO, Kreer C, and Klein F (2022). Antibody-mediated neutralization of SARS-CoV-2. Immunity55, 925-944. doi:10.1016/j.immuni.2022.05.005.
  • Kretschmer AC, Junker L, Dewald F, Linne V, Hennen L, Horemheb-Rubio G, Kaiser R, Steger G, Joachim A, Schonenkorb J, Cosgun ZC, Muhlhans N, Heger E, Knops E, Leisse C, Kessel B, Heinsohn T, Rodiah I, Lange B, Ritter AL, Fries M, Kossow A, Niessen J, Dotsch J, Klein F, Rybniker J, Fatkenheuer G, and Suarez I (2022). Implementing the Lolli-Method and pooled RT-qPCR testing for SARS-CoV-2 surveillance in schools: a pilot project. Infection. doi:10.1007/s15010-022-01865-0.
  • Gruell H, Vanshylla K, Tober-Lau P, Hillus D, Schommers P, Lehmann C, Kurth F, Sander LE, and Klein F (2022). mRNA booster immunization elicits potent neutralizing serum activity against the SARS-CoV-2 Omicron variant. Nat Med28, 477-480. doi:10.1038/s41591-021-01676-0.
  • Vanshylla K, Tober-Lau P, Gruell H, Munn F, Eggeling R, Pfeifer N, Le NH, Landgraf I, Kurth F, Sander LE, and Klein F (2022). Durability of omicron-neutralising serum activity after mRNA booster immunisation in older adults. Lancet Infect Dis22, 445-446. doi:10.1016/S1473-3099(22)00135-9.
  • Eberhardt KA, Dewald F, Heger E, Gieselmann L, Vanshylla K, Wirtz M, Kleipass F, Johannis W, Schommers P, Gruell H, Brensing KA, Muller RU, Augustin M, Lehmann C, Koch M, Klein F, and Di Cristanziano V (2021). Evaluation of a New Spike (S)-Protein-Based Commercial Immunoassay for the Detection of Anti-SARS-CoV-2 IgG. Microorganisms9. doi:10.3390/microorganisms9040733.
  • Halwe S, Kupke A, Vanshylla K, Liberta F, Gruell H, Zehner M, Rohde C, Krahling V, Gellhorn Serra M, Kreer C, Kluver M, Sauerhering L, Schmidt J, Cai Z, Han F, Young D, Yang G, Widera M, Koch M, Werner A, Kamper L, Becker N, Marlow MS, Eickmann M, Ciesek S, Schiele F, Klein F, and Becker S (2021). Intranasal Administration of a Monoclonal Neutralizing Antibody Protects Mice against SARS-CoV-2 Infection. Viruses13. doi:10.3390/v13081498.
  • Horn C, Augustin M, Ercanoglu MS, Heger E, Knops E, Bondet V, Duffy D, Chon SH, Nierhoff D, Oette M, Schafer H, Vivaldi C, Held K, Anderson J, Geldmacher C, Suarez I, Rybniker J, Klein F, Fatkenheuer G, Muller-Trutwin M, and Lehmann C (2021). HIV DNA reservoir and elevated PD-1 expression of CD4 T-cell subsets particularly persist in the terminal ileum of HIV-positive patients despite cART. HIV Med22, 397-408. doi:10.1111/hiv.13031.
  • Korenkov M, Poopalasingam N, Madler M, Vanshylla K, Eggeling R, Wirtz M, Fish I, Dewald F, Gieselmann L, Lehmann C, Fatkenheuer G, Gruell H, Pfeifer N, Heger E, and Klein F (2021). Evaluation of a Rapid Antigen Test To Detect SARS-CoV-2 Infection and Identify Potentially Infectious Individuals. J Clin Microbiol59, e0089621. doi:10.1128/JCM.00896-21.
  • Meijers M, Vanshylla K, Gruell H, Klein F, and Lassig M (2021). Predicting in vivo escape dynamics of HIV-1 from a broadly neutralizing antibody. Proc Natl Acad Sci U S A118. doi:10.1073/pnas.2104651118.
  • Theobald SJ, Simonis A, Georgomanolis T, Kreer C, Zehner M, Eisfeld HS, Albert MC, Chhen J, Motameny S, Erger F, Fischer J, Malin JJ, Grab J, Winter S, Pouikli A, David F, Boll B, Koehler P, Vanshylla K, Gruell H, Suarez I, Hallek M, Fatkenheuer G, Jung N, Cornely OA, Lehmann C, Tessarz P, Altmuller J, Nurnberg P, Kashkar H, Klein F, Koch M, and Rybniker J (2021). Long-lived macrophage reprogramming drives spike protein-mediated inflammasome activation in COVID-19. EMBO Mol Med13, e14150. doi:10.15252/emmm.202114150.
  • Vanshylla K, Di Cristanziano V, Kleipass F, Dewald F, Schommers P, Gieselmann L, Gruell H, Schlotz M, Ercanoglu MS, Stumpf R, Mayer P, Zehner M, Heger E, Johannis W, Horn C, Suarez I, Jung N, Salomon S, Eberhardt KA, Gathof B, Fatkenheuer G, Pfeifer N, Eggeling R, Augustin M, Lehmann C, and Klein F (2021). Kinetics and correlates of the neutralizing antibody response to SARS-CoV-2 infection in humans. Cell Host Microbe29, 917-929 e914. doi:10.1016/j.chom.2021.04.015.
  • Vanshylla K, Fan C, Wunsch M, Poopalasingam N, Meijers M, Kreer C, Kleipass F, Ruchnewitz D, Ercanoglu MS, Gruell H, Munn F, Pohl K, Janicki H, Nolden T, Bartl S, Stein SC, Augustin M, Dewald F, Gieselmann L, Schommers P, Schulz TF, Sander LE, Koch M, Luksza M, Lassig M, Bjorkman PJ, and Klein F (2021). Discovery of ultrapotent broadly neutralizing antibodies from SARS-CoV-2 elite neutralizers. Cell Host Microbe. doi:10.1016/j.chom.2021.12.010.
  • Vanshylla K, Held K, Eser TM, Gruell H, Kleipass F, Stumpf R, Jain K, Weiland D, Munch J, Gruttner B, Geldmacher C, and Klein F (2021). CD34T+ Humanized Mouse Model to Study Mucosal HIV-1 Transmission and Prevention. Vaccines (Basel)9. doi:10.3390/vaccines9030198.
  • Weber T, Potthoff J, Bizu S, Labuhn M, Dold L, Schoofs T, Horning M, Ercanoglu MS, Kreer C, Gieselmann L, Vanshylla K, Langhans B, Janicki H, Stroh LJ, Knops E, Nierhoff D, Spengler U, Kaiser R, Bjorkman PJ, Krey T, Bankwitz D, Pfeifer N, Pietschmann T, Flyak AI, and Klein F (2021). Analysis of antibodies from HCV elite neutralizers identifies genetic determinants of broad neutralization. Immunity. doi:10.1016/j.immuni.2021.12.003.
  • Wennhold K, Thelen M, Lehmann J, Schran S, Preugszat E, Garcia-Marquez M, Lechner A, Shimabukuro-Vornhagen A, Ercanoglu MS, Klein F, Thangarajah F, Eidt S, Loser H, Bruns C, Quaas A, von Bergwelt-Baildon M, and Schlosser HA (2021). CD86(+) Antigen-Presenting B Cells Are Increased in Cancer, Localize in Tertiary Lymphoid Structures, and Induce Specific T-cell Responses. Cancer Immunol Res9, 1098-1108. doi:10.1158/2326-6066.CIR-20-0949.
  • Wunsch M, Aschemeier D, Heger E, Ehrentraut D, Kruger J, Hufbauer M, Syed AS, Horemheb-Rubio G, Dewald F, Fish I, Schlotz M, Gruell H, Augustin M, Lehmann C, Kaiser R, Knops E, Silling S, and Klein F (2021). Safe and effective pool testing for SARS-CoV-2 detection. J Clin Virol145, 105018. doi:10.1016/j.jcv.2021.105018.
  • Gieselmann L, Kreer C, Ercanoglu MS, Lehnen N, Zehner M, Schommers P, Potthoff J, Gruell H, and Klein F (2021). Effective high-throughput isolation of fully human antibodies targeting infectious pathogens. Nat Protoc16, 3639-3671. doi:10.1038/s41596-021-00554-w.
  • Augustin M, Schommers P, Suarez I, Koehler P, Gruell H, Klein F, Maurer C, Langerbeins P, Priesner V, Schmidt-Hellerau K, Malin JJ, Stecher M, Jung N, Wiesmuller G, Meissner A, Zweigner J, Langebartels G, Kolibay F, Suarez V, Burst V, Valentin P, Schedler D, Cornely OA, Hallek M, Fatkenheuer G, Rybniker J, and Lehmann C (2020). Rapid response infrastructure for pandemic preparedness in a tertiary care hospital: lessons learned from the COVID-19 outbreak in Cologne, Germany, February to March 2020. Euro Surveill 25.
     
  • Cohen-Dvashi H, Zehner M, Ehrhardt S, Katz M, Elad N, Klein F, and Diskin R (2020). Structural Basis for a Convergent Immune Response against Ebola Virus. Cell Host Microbe 27, 418-27 e4.
  • Eberhardt KA, Meyer-Schwickerath C, Heger E, Knops E, Lehmann C, Rybniker J, Schommers P, Eichenauer DA, Kurth F, Ramharter M, Kaiser R, Holtick U, Klein F, Jung N, and Di Cristanziano V (2020). RNAemia Corresponds to Disease Severity and Antibody Response in Hospitalized COVID-19 Patients. Viruses 12.
     
  • Heidepriem J, Krahling V, Dahlke C, Wolf T, Klein F, Addo MM, Becker S, and Loeffler FF (2020). Epitopes of Naturally Acquired and Vaccine-induced Anti-Ebola Virus Glycoprotein Antibodies in Single Amino Acid Resolution. Biotechnol J 10.1002/biot.202000069, e2000069.
     
  • Kreer C, Doring M, Lehnen N, Ercanoglu MS, Gieselmann L, Luca D, Jain K, Schommers P, Pfeifer N, and Klein F (2020a). openPrimeR for multiplex amplification of highly diverse templates. J Immunol Methods 480, 112752.
  • Kreer C, Zehner M, Weber T, Ercanoglu MS, Gieselmann L, Rohde C, Halwe S, Korenkov M, Schommers P, Vanshylla K, Di Cristanziano V, Janicki H, Brinker R, Ashurov A, Krahling V, Kupke A, Cohen-Dvashi H, Koch M, Eckert JM, Lederer S, Pfeifer N, Wolf T, Vehreschild MJGT, Wendtner C, Diskin R, Gruell H, Becker S, and Klein F (2020c). Longitudinal Isolation of Potent Near-Germline SARS-CoV-2-Neutralizing Antibodies from COVID-19 Patients. Cell 182, 843-+.
     
  • Luers JC, Rokohl AC, Loreck N, Wawer Matos PA, Augustin M, Dewald F, Klein F, Lehmann C, and Heindl LM (2020). Olfactory and Gustatory Dysfunction in Coronavirus Disease 2019 (COVID-19). Clin Infect Dis71, 2262-2264. doi:10.1093/cid/ciaa525
  • Niessl J, Baxter AE, Mendoza P, Jankovic M, Cohen YZ, Butler AL, Lu CL, Dube M, Shimeliovich I, Gruell H, Klein F, Caskey M, Nussenzweig MC, and Kaufmann DE (2020). Combination anti-HIV-1 antibody therapy is associated with increased virus-specific T cell immunity. Nat Med 26, 222-7.
     
  • Ramani A, Muller L, Ostermann PN, Gabriel E, Abida-Islam P, Muller-Schiffmann A, Mariappan A, Goureau O, Gruell H, Walker A, Andree M, Hauka S, Houwaart T, Dilthey A, Wohlgemuth K, Omran H, Klein F, Wieczorek D, Adams O, Timm J, Korth C, Schaal H, and Gopalakrishnan J (2020). SARS-CoV-2 targets neurons of 3D human brain organoids. EMBO J 39, e106230.
     
  • Schermer B, Fabretti F, Damagnez M, Di Cristanziano V, Heger E, Arjune S, Tanner NA, Imhof T, Koch M, Ladha A, Joung J, Gootenberg JS, Abudayyeh OO, Burst V, Zhang F, Klein F, Benzing T, and Muller RU (2020). Rapid SARS-CoV-2 testing in primary material based on a novel multiplex RT-LAMP assay. PloS one 15, e0238612.
     
  • Schommers P, Gruell H, Abernathy ME, Tran MK, Dingens AS, Gristick HB, Barnes CO, Schoofs T, Schlotz M, Vanshylla K, Kreer C, Weiland D, Holtick U, Scheid C, Valter MM, van Gils MJ, Sanders RW, Vehreschild JJ, Cornely OA, Lehmann C, Fatkenheuer G, Seaman MS, Bloom JD, Bjorkman PJ, and Klein F (2020). Restriction of HIV-1 Escape by a Highly Broad and Potent Neutralizing Antibody. Cell 180, 471-89 e22.
  • Theobald SJ, Kreer C, Khailaie S, Bonifacius A, Eiz-Vesper B, Figueiredo C, Mach M, Backovic M, Ballmaier M, Koenig J, Olbrich H, Schneider A, Volk V, Danisch S, Gieselmann L, Ercanoglu MS, Messerle M, Kaisenberg CV, Witte T, Klawonn F, Meyer-Hermann M, Klein F, and Stripecke R (2020). Repertoire characterization and validation of gB-specific human IgGs directly cloned from humanized mice vaccinated with dendritic cells and protected against HCMV. PLoS pathogens 16, e1008560.
  • Kreer C, Gruell H, Mora T, Walczak AM, and Klein F (2020). Exploiting B Cell Receptor Analyses to Inform on HIV-1 Vaccination Strategies. Vaccines (Basel)8. doi:10.3390/vaccines8010013.
                      • Stecher M, Classen A, Klein F, Lehmann C, Gruell H, Platten M, Wyen C, Behrens G, Fatkenheuer G, and Vehreschild JJ (2020). Systematic Review and Meta-analysis of Treatment Interruptions in Human Immunodeficiency Virus (HIV) Type 1-infected Patients Receiving Antiretroviral Therapy: Implications for Future HIV Cure Trials. Clin Infect Dis70, 1406-1417. doi:10.1093/cid/ciz417.
                      Prof. Dr. Florian Klein CMMC Cologne
                      Prof. Dr. Florian Klein

                      Center for Molecular Medicine Cologne | Institute of Virology | CMMC Research Building

                      CMMC - PI - assoc. RG 10

                      Executive Board Member

                      +49 221 478 89693

                      +49 221 478 3904

                      Center for Molecular Medicine Cologne | Institute of Virology | CMMC Research Building

                      Robert-Koch-Str. 21

                      50931 Cologne

                      https://klein-lab.de/

                      CMMC Profile Page

                      Curriculum Vitae (CV)

                      Publications on PubMed

                      Curriculum Vitae - Florian Klein
                      Publications - Florian Klein

                      Link to PubMed

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                      University of Cologne (Universtität zu Köln)
                      Faculty of Medicine Faculty of Mathematics
                      and Natural Sciences
                      University Hospital of Cologne (Universitätsklinik zu Köln)

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                      Prof. Dr. med. Thomas Benzing
                      Chair of the CMMC