Project B1

Predicting viral escape as a consequence of antibody-mediated selection pressure

Florian Klein, U Cologne | web | email

In this project, we aim to identify common principles to predict viral selection and evolution upon humoral immunity against HIV-1, Influenza A virus, and SARS-CoV-2.
To this end, we perform high-throughput pseudovirus neutralization assays to identify viral escape patterns to single monoclonal antibodies, as well as polyclonal immunoglobulins isolated from infected or vaccinated individuals.
By closely collaborating with the projects B2, B5, and Z2, we expect to inform on the emergence of future viral variants as well as on strategies to prevent viral escape from neutralizing antibodies.

Predictability in Evolution

Collaborative Research Center 1310

Publications

Somatic hypermutation introduces bystander mutations that prepare SARS-CoV-2 antibodies for emerging variants

Korenkov M., Zehner M., Cohen-Dvashi H., Borenstein-Katz A., Kottege L., Janicki H., Vanshylla K., Weber T., Gruell H., Koch M., Diskin R., Kreer C., Klein F., Cell Immunity 1074-7613, 29. November 2023, https://doi.org/10.1016/j.immuni.2023.11.004

Enhanced SARS-CoV-2 humoral immunity following breakthrough infection builds upon the preexisting memory B cell pool

Weber T., Dähling S., Rose S., Affeldt P., Vanshylla K., Ullrich L., Gieselmann L., Teipel F., Gruell H., Di Cristanziano V., Kim D.S., Georgiou G., Koch M., Kreer C., Klein F., Sci. Immunol.8, eadk5845, 17. November 2023, https://doi.org/10.1126/sciimmunol.adk5845

Probabilities of developing HIV-1 bNAb sequence features in uninfected and chronically infected individuals

Kreer C., Lupo C, Ercanoglu M.S., Gieselmann L., Spisak N., Grossbach J., Schlotz M., Schommers P., Gruell H., Dold L., Beyer A., Nourmohammad A., Mora T., Walczak A.M., Klein F., Nat Commun 14(7137), 6. November 2023, https://doi.org/10.1038/s41467-023-42906-y

Pausing methotrexate prevents impairment of Omicron BA.1 and BA.2 neutralisation after COVID-19 booster vaccination

Habermann E., Gieselmann L., Tober-Lau P., Klotsche J., Albach F.N., Ten Hagen A., Zernicke J., Ahmadov E., Arumahandi de Silva A.N., Frommert L.M., Kurth F., Sander L.E., Burmester G.R., Klein F., Biesen R, RMD Open, 12. September 2022, https://doi.org/10.1136/rmdopen-2022-002639

Design of an optimal combination therapy with broadly neutralizing antibodies to suppress HIV-1

LaMont C., Otwinowski J., Vanshylla K., Gruell H., Klein F., Nourmohammad A., eLife, 19. July 2022, https://doi.org/10.7554/eLife.76004

SARS-CoV-2 Omicron sublineages exhibit distinct antibody escape patterns

Gruell H., Vanshylla K., Korenkov M., Tober-Lau P., Zehner M., Münn F., Janicki H., Augustin M., Schommers P., Sander L.E., Kurth F., Kreer C., Klein F., Cell Host Microbe, 7. July 2022, https://doi.org/10.1016/j.chom.2022.07.002

Effective high-throughput RT-qPCR screening for SARS-CoV-2 infections in children

Dewald F., Suárez I., Johnen R., Grossbach J., Moran-Tovar R., Steger G., Joachim A., Rubio G.H., Fries M. , Behr F., Kley J., Lingnau A., Kretschmer A., Gude C., Baeza-Flores G., Laveaga del Valle D., Roblero-Hernandez A., Magana-Cerino J., Hernandez A.T., Ruiz-Quinones J., Schega K., Linne V., Junker L., Wunsch M., Heger E., Knops E., Di Cristanziano V., Meyer M., Hünseler C., Weber L.T., Lüers L.C., Quade G., Wisplinghoff H., Tiemann C., Zotz R., Jomaa H., Pranada A., Herzum I., Cullen P., Schmitz F.J., Philipsen P., Kirchner G., Knabbe C., Hellmich M., Buess M., Wolff A., Kossow A., Niessen J., Jeworutzki S., Schräpler J.-P., Lässig M., Dötsch J., Fätkenheuer D., Kaiser R., Beyer A., Rybniker J., Klein F., Nature Communications, 25. June 2022, https://www.nature.com/articles/s41467-022-30664-2

Cross-Variant Neutralizing Serum Activity after SARS-CoV-2 Breakthrough Infections

Tober-Lau P., Gruell H., Vanshylla K., Koch W.M., Hillus D., Schommers P., Suárez I., Suttorp N., Sander L.E., Klein F., Kurth F., Emerg Infect Dis, 5. May 2022, https://doi.org/10.3201/eid2805.220271

No substantial preexisting B cell immunity against SARS-CoV-2 in healthy adults

Ercanoglu M.S., Gieselmann L., Dähling S., Poopalasingam N., Detmer S., Koch M., Korenkov M., Halwe S., Klüver M., Di Cristanziano V., Janicki H., Schlotz M., Worczinski J., Gathof B., Gruell H., Zehner M., Becker S., Vanshylla K., Kreer C., Klein F., iScience, 3. March 2022, https://doi.org/10.1016/j.isci.2022.103951

Discovery of ultrapotent broadly neutralizing antibodies from SARS-CoV-2 elite neutralizers

Vanshylla K., Fan C., Wunsch M., Poopalasingam N., Meijers M., Kreer C., Kleipass F., Ruchnewitz D., Ercanoglu M.S., Gruell H., Münn F., Pohl K., Janicki H., Nolden T., Bartl S., Stein S.C., Augustin M., Dewald F., Gieselmann L., Schommers P., Schulz T.F., Sander L.E., Koch M., Łuksza M., Lässig M., Bjorkman P.J., Klein F., Cell Host Microbe, 12. January 2022, https://doi.org/10.1016/j.chom.2021.12.010

Effective high-throughput isolation of fully human antibodies targeting infectious pathogens

Gieselmann L., Kreer C., Ercanoglu M.S., Lehnen N., Zehner M., Schommers P., Potthoff J., Gruell H., Klein F., Nat Protoc, 25. May 2021, https://doi.org/10.1038/s41596-021-00554-w

Kinetics and correlates of the neutralizing antibody response to SARS-CoV-2 infection in humans

Vanshylla K., Di Cristanziano V., Kleipass F., Dewald F., Schommers P., Gieselmann L., Gruell H., Schlotz M., Ercanoglu M.S., Stumpf R., Mayer P., Zehner M., Heger E., Johannis W., Horn C., Suárez I., Jung N., Salomon S., Eberhardt K.A., Gathof B., Fätkenheuer G., Pfeifer N., Eggeling R., Augustin M., Lehmann C., Klein F., Cell Host Microbe, 28. April 2021, https://doi.org/10.1016/j.chom.2021.04.015

Evaluation of a New Spike (S)-Protein-Based Commercial Immunoassay for the Detection of Anti-SARS-CoV-2 IgG

Eberhardt K.A., Dewald F., Heger E., Gieselmann L., Vanshylla K., Wirtz M., Kleipass F., Johannis W., Schommers P., Gruell H., Brensing K.A., Müller R.U., Augustin M., Lehmann C., Koch M., Klein F., Di Cristanziano V., Microorganisms, 31. March 2021, https://doi.org/10.3390/microorganisms9040733

CD34T+ Humanized Mouse Model to Study Mucosal HIV-1 Transmission and Prevention

Vanshylla K., Held K., Eser T.M., Gruell H., Kleipass F., Stumpf R., Jain K., Weiland D., Münch J., Grüttner B., Geldmacher C., Klein F., Vaccines (Basel) 9(3):198, 27. February 2021, https://doi.org/10.3390/vaccines9030198

Longitudinal Isolation of Potent Near-Germline SARS-CoV-2-Neutralizing Antibodies from COVID-19 Patients

Kreer C., Zehner M., Weber T., Ercanoglu M.S., Gieselmann L., Rohde C., Halwe S., Korenkov M., Schommers P., Vanshylla K., Di Cristanziano V., Janicki H., Brinker R., Ashurov A., Krähling V., Kupke A., Cohen-Dvashi H., Koch M, Eckert J.M., Lederer S., Pfeifer N., Wolf T., Vehreschild M.J.G.T., Wendtner C., Diskin R., Gruell H., Becker S., Klein F., Cell 182(4):843-854.e12., 20. August 2020, https://doi.org/10.1016/j.cell.2020.06.044

Repertoire characterization and validation of gB-specific human IgGs directly cloned from humanized mice vaccinated with dendritic cells and protected against HCMV

Theobald S.J., 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 M.S., Messerle M., Kaisenberg C.V., Witte T., Klawonn F., Meyer-Hermann M., Klein F., Stripecke R., Pathog 16(7):e1008560, 15. July 2020, https://doi.org/10.1371/journal.ppat.1008560

Structural Basis for a Convergent Immune Response against Ebola Virus

Cohen-Dvashi H., Zehner M., Ehrhardt S., Katz M., Elad N., Klein F., Diskin R., Cell Host Microbe. 27(3):418-427.e4., 11. March 2020, https://doi.org/10.1016/j.chom.2020.01.007

Antibody Teamwork against Ebola Virus Disease

Zehner M., Klein F., Immunity. 52(2):217-219, 18. February 2020, https://doi.org/10.1016/j.immuni.2020.01.016

Restriction of HIV-1 Escape by a Highly Broad and Potent Neutralizing Antibody

Schommers P., Gruell H., Abernathy M.E., Tran M.K., Dingens A.S., Gristick H.B., Barnes C.O., Schoofs T., Schlotz M., Vanshylla K., Kreer C., Weiland D., Holtick U., Scheid C., Valter M.M., van Gils M.J., Sanders R.W., Vehreschild J.J., Cornely O.A., Lehmann C., Fätkenheuer G., Seaman M.S., Bloom J.D., Bjorkman P.J., Klein F., Cell 180(3):471-489.e22, 6. February 2020, https://doi.org/10.1016/j.cell.2020.01.010

openPrimeR for multiplex amplification of highly diverse templates

Kreer C., Döring M., Lehnen N., Ercanoglu M.S., Gieselmann L., Luca D., Jain K., Schommers P., Pfeifer N., Klein F., J Immunol Methods. 480:112752, 25. January 2020, https://doi.org/10.1016/j.jim.2020.112752

Exploiting B Cell Receptor Analyses to Inform on HIV-1 Vaccination Strategies

Kreer C., Gruell H., Mora T., Walczak A.M., Klein F., Vaccines 8(1) 13, 1. January 2020, https://doi.org/10.3390/vaccines8010013

Polyclonal and convergent antibody response to Ebola virus vaccine rVSV-ZEBOV

Ehrhardt S.A., Zehner M., Krähling V., Cohen-Dvashi H., Kreer C., Elad N., Gruell H., Ercanoglu M.S., Schommers P., Gieselmann L., Eggeling R., Dahlke C., Wolf T., Pfeifer N., Addo M.M., Diskin R., Becker S., Klein F., Nat Med. 25(10):1589-1600., 7. October 2019, https://doi.org/10.1038/s41591-019-0602-4

Modeling the Amplification of Immunoglobulins through Machine Learning on Sequence-Specific Features

Döring M., Kreer C., Lehnen N., Klein F., Pfeifer N., Sci Rep. 9(1):10748., 24. July 2019, https://doi.org/10.1038/s41598-019-47173-w

Antibody 10-1074 suppresses viremia in HIV-1-infected individuals

Caskey M., Schoofs T., Gruell H., Settler A., Karagounis T., …, Klein F., Nat Med 23, 185-191, 16. January 2017, http://dx.doi.org/10.1038/nm.4268

HIV-1 therapy with monoclonal antibody 3BNC117 elicits host immune responses against HIV-1

Schoofs T., Klein F., Braunschweig M., Kreider E.F., Feldmann A. et al., Science 352: 997-1001, 20. May 2016, https://doi.org/10.1126/science.aaf0972

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