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2. CoPoP liposomes displaying stabilized clade C HIV-1 Env elicit tier 2 multiclade neutralization in rabbits

Author

Koornneef, Annemart, Vanshylla, Kanika, Hardenberg, Gijs, Rutten, Lucy, Strokappe, Nika M., Tolboom, Jeroen, Vreugdenhil, Jessica, Boer, Karin Feddes-de, Perkasa, Aditya, Blokland, Sven, Burger, Judith A., Huang, Wei-Chiao, Lovell, Jonathan F., van Manen, Danielle, Sanders, Rogier W., Zahn, Roland C., Schuitemaker, Hanneke, Langedijk, Johannes P. M., and Wegmann, Frank

Published
2024
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3. Design of an optimal combination therapy with broadly neutralizing antibodies to suppress HIV-1

Author

LaMont, Colin, Otwinowski, Jakub, Vanshylla, Kanika, Gruell, Henning, Klein, Florian, and Nourmohammad, Armita

Subjects
Quantitative Biology - Populations and Evolution
Abstract

Broadly neutralizing antibodies (bNAbs) are promising targets for vaccination and therapy against HIV. Passive infusions of bNAbs have shown promise in clinical trials as a potential alternative for anti-retroviral therapy. A key challenge for the potential clinical application of bnAbs is the suppression of viral escape, which is more effectively achieved with a combination of bNAbs. However, identifying an optimal bNAb cocktail is combinatorially complex. Here, we propose a computational approach to predict the efficacy of a bNAb therapy trial based on the population genetics of HIV escape, which we parametrize using high-throughput HIV sequence data from a cohort of untreated bNAb-naive patients. By quantifying the mutational target size and the fitness cost of HIV-1 escape from bNAbs, we reliably predict the distribution of rebound times in three clinical trials. Importantly, we show that early rebounds are dominated by the pre-treatment standing variation of HIV-1 populations, rather than spontaneous mutations during treatment. Lastly, we show that a cocktail of three bNAbs is necessary to suppress the chances of viral escape below 1%, and we predict the optimal composition of such a bNAb cocktail. Our results offer a rational design for bNAb therapy against HIV-1, and more generally show how genetic data could be used to predict treatment outcomes and design new approaches to pathogenic control.

Published
2021

4. Nucleocapsid-specific T cell responses associate with control of SARS-CoV-2 in the upper airways before seroconversion

Author

Eser, Tabea M., Baranov, Olga, Huth, Manuel, Ahmed, Mohammed I. M., Deák, Flora, Held, Kathrin, Lin, Luming, Pekayvaz, Kami, Leunig, Alexander, Nicolai, Leo, Pollakis, Georgios, Buggert, Marcus, Price, David A., Rubio-Acero, Raquel, Reich, Jakob, Falk, Philine, Markgraf, Alissa, Puchinger, Kerstin, Castelletti, Noemi, Olbrich, Laura, Vanshylla, Kanika, Klein, Florian, Wieser, Andreas, Hasenauer, Jan, Kroidl, Inge, Hoelscher, Michael, and Geldmacher, Christof

Published
2023
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5. Predicting in vivo escape dynamics of HIV-1 from a broadly neutralizing antibody

Author

Meijers, Matthijs, Vanshylla, Kanika, Gruell, Henning, Klein, Florian, and Laessig, Michael

Subjects
Quantitative Biology - Populations and Evolution
Abstract

Broadly neutralizing antibodies are promising candidates for treatment and prevention of HIV-1 infections. Such antibodies can temporarily suppress viral load in infected individuals; however, the virus often rebounds by escape mutants that have evolved resistance. In this paper, we map an in vivo fitness landscape of HIV-1 interacting with broadly neutralizing antibodies, using data from a recent clinical trial. We identify two fitness factors, antibody dosage and viral load, that determine viral reproduction rates reproducibly across different hosts. The model successfully predicts the escape dynamics of HIV-1 in the course of an antibody treatment, including a characteristic frequency turnover between sensitive and resistant strains. This turnover is governed by a dosage-dependent fitness ranking, resulting from an evolutionary tradeoff between antibody resistance and its collateral cost in drug-free growth. Our analysis suggests resistance-cost tradeoff curves as a measure of antibody performance in the presence of resistance evolution., Comment: 16 pages, 6 figures

Published
2020
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10. Safety, reactogenicity, and immunogenicity of homologous and heterologous prime-boost immunisation with ChAdOx1 nCoV-19 and BNT162b2: a prospective cohort study

Author

Al-Rim, Ben, Bardtke, Lara, Beheim-Schwarzbach, Jörn Ilmo, Behn, Kerstin, Bergfeld, Leon, Bethke, Norma, Bleicker, Tobias, Briesemeister, Dana, Brumhard, Sophia, Conrad, Claudia, Dieckmann, Sebastian, Frey, Doris, Gabelich, Julie-Anne, Georg, Philipp, Gläser, Ute, Hasler, Lisbeth, Hetey, Andreas, Hiller, Anna Luisa, Horn, Alexandra, Hülso, Claudia, Kegel, Luisa, Koch, Willi, Krannich, Alexander, Kroneberg, Paolo, Lisy, Michelle, Mackeldanz, Petra, Maeß, Birgit, Münn, Friederike, Olk, Nadine, Peiser, Christian, Pohl, Kai, Hermel, Annelie, Rönnefarth, Maria, Rubisch, Carolin, Sanchez Rezza, Angela, Schellenberger, Isabelle, Schenkel, Viktoria, Schlesinger, Jenny, Schmidt, Sein, Schwanitz, Georg, Sinnigen, Anne-Sophie, Stubbemann, Paula, Tesch, Julia, Treue, Denise, Wendisch, Daniel, Zvorc, Saskia, Hillus, David, Schwarz, Tatjana, Tober-Lau, Pinkus, Vanshylla, Kanika, Hastor, Hana, Thibeault, Charlotte, Jentzsch, Stefanie, Helbig, Elisa T, Lippert, Lena J, Tscheak, Patricia, Schmidt, Marie Luisa, Riege, Johanna, Solarek, André, von Kalle, Christof, Dang-Heine, Chantip, Gruell, Henning, Kopankiewicz, Piotr, Suttorp, Norbert, Drosten, Christian, Bias, Harald, Seybold, Joachim, Klein, Florian, Kurth, Florian, Corman, Victor Max, and Sander, Leif Erik

Published
2021
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11. Cross-Variant Neutralizing Serum Activity after SARS-CoV-2 Breakthrough Infections

Author

Tober-Lau, Pinkus, Gruell, Henning, Vanshylla, Kanika, Koch, Willi M., Hillus, David, Schommers, Philipp, Suarez, Isabelle, Suttorp, Norbert, Sander, Leif Erik, Klein, Florian, and Kurth, Florian

Subjects
Health
Abstract

The B.1.1.529 (Omicron) variant of concern of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) carries a high number of nonsynonymous mutations in the spike glycoprotein, relative to that of the [...]

Published
2022
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12. Long‐lived macrophage reprogramming drives spike protein‐mediated inflammasome activation in COVID‐19

Author

Theobald, Sebastian J, Simonis, Alexander, Georgomanolis, Theodoros, Kreer, Christoph, Zehner, Matthias, Eisfeld, Hannah S, Albert, Marie‐Christine, Chhen, Jason, Motameny, Susanne, Erger, Florian, Fischer, Julia, Malin, Jakob J, Gräb, Jessica, Winter, Sandra, Pouikli, Andromachi, David, Friederike, Böll, Boris, Koehler, Philipp, Vanshylla, Kanika, Gruell, Henning, Suárez, Isabelle, Hallek, Michael, Fätkenheuer, Gerd, Jung, Norma, Cornely, Oliver A, Lehmann, Clara, Tessarz, Peter, Altmüller, Janine, Nürnberg, Peter, Kashkar, Hamid, Klein, Florian, Koch, Manuel, and Rybniker, Jan

Published
2021
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13. Spermine and spermidine bind CXCR4 and inhibit CXCR4- but not CCR5-tropic HIV-1 infection

Author

Harms, Mirja, primary, Smith, Nikaïa, additional, Han, Mingyu, additional, Groß, Rüdiger, additional, von Maltitz, Pascal, additional, Stürzel, Christina, additional, Ruiz-Blanco, Yasser B., additional, Almeida-Hernández, Yasser, additional, Rodriguez-Alfonso, Armando, additional, Cathelin, Dominique, additional, Caspar, Birgit, additional, Tahar, Bouceba, additional, Sayettat, Sophie, additional, Bekaddour, Nassima, additional, Vanshylla, Kanika, additional, Kleipass, Franziska, additional, Wiese, Sebastian, additional, Ständker, Ludger, additional, Klein, Florian, additional, Lagane, Bernard, additional, Boonen, Arnaud, additional, Schols, Dominique, additional, Benichou, Serge, additional, Sanchez-Garcia, Elsa, additional, Herbeuval, Jean-Philippe, additional, and Münch, Jan, additional

Published
2023
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14. Dissecting the impact of somatic hypermutation on SARS-CoV-2 neutralization and viral escape

Author

Korenkov, Michael, primary, Zehner, Matthias, additional, Cohen-Dvashi, Hadas, additional, Borenstein-Katz, Aliza, additional, Kottege, Lisa, additional, Janicki, Hanna, additional, Vanshylla, Kanika, additional, Weber, Timm, additional, Gruell, Henning, additional, Koch, Manuel, additional, Diskin, Ron, additional, Kreer, Christoph, additional, and Klein, Florian, additional

Published
2023
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15. Short- and long-term T cell and antibody responses following dexamethasone treatment in COVID-19

Author

Thibeault, Charlotte, primary, Bardtke, Lara, additional, Vanshylla, Kanika, additional, di Cristanziano, Veronica, additional, Eberhardt, Kirsten A., additional, Stubbemann, Paula, additional, Hillus, David, additional, Tober-Lau, Pinkus, additional, Mukherjee, Parnika, additional, Münn, Friederike, additional, Lippert, Lena J., additional, Helbig, Elisa T., additional, Lingscheid, Tilman, additional, Steinbeis, Fridolin, additional, Mittermaier, Mirja, additional, Witzenrath, Martin, additional, Zoller, Thomas, additional, Klein, Florian, additional, Sander, Leif E., additional, and Kurth, Florian, additional

Published
2023
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16. Enhanced SARS-CoV-2 humoral immunity following breakthrough infection builds upon the preexisting memory B cell pool.

Author

Weber, Timm, Dähling, Sabrina, Rose, Svea, Affeldt, Patrick, Vanshylla, Kanika, Ullrich, Leon, Gieselmann, Lutz, Teipel, Finn, Gruell, Henning, Di Cristanziano, Veronica, Kim, Dae Sung, Georgiou, George, Koch, Manuel, Kreer, Christoph, and Klein, Florian

Subjects
IMMUNOLOGIC memory, BREAKTHROUGH infections, HUMORAL immunity, SARS-CoV-2, BOOSTER vaccines
Abstract

The human immune response must continuously adapt to newly emerging SARS-CoV-2 variants. To investigate how B cells respond to repeated SARS-CoV-2 antigen exposure by Wu01 booster vaccination and Omicron breakthrough infection, we performed a molecular longitudinal analysis of the memory B cell pool. We demonstrate that a subsequent breakthrough infection substantially increases the frequency of B cells encoding SARS-CoV-2–neutralizing antibodies. However, this is not primarily attributable to maturation, but to selection of preexisting B cell clones. Moreover, broadly reactive memory B cells arose early and even neutralized highly mutated variants like XBB.1.5 that the individuals had not encountered. Together, our data show that SARS-CoV-2 immunity is largely imprinted on Wu01 over the course of multiple antigen contacts but can respond to new variants through preexisting diversity. Editor's summary: As the immune system is exposed to new SARS-CoV-2 variants, it must rapidly adapt, but how repeated antigen contacts influence the evolution of SARS-CoV-2–specific memory B cells is not well defined. Weber et al. explored how third dose SARS-CoV-2 vaccination and subsequent Omicron breakthrough infection influenced antibody and memory B cell responses. Serum antibodies had enhanced neutralization capacity after third dose vaccination. However, the SARS-CoV-2–specific memory B cell pool was significantly expanded only in individuals with a breakthrough infection after third dose. This was due to selection of pre-existing Omicron-neutralizing memory B cells that potently neutralized a broad range of variants that arose after initial vaccination. These findings demonstrate that SARS-CoV-2 immunity is imprinted during early antigen exposure and adapts to new variants. —Hannah Isles [ABSTRACT FROM AUTHOR]

Published
2023
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17. Early nucleocapsid-specific T cell responses associate with control of SARS-CoV-2 in the upper airways and reduced systemic inflammation before seroconversion

Author

Eser, Tabea M., primary, Baranov, Olga, additional, Huth, Manuel, additional, Ahmed, Mohamed I. M., additional, Deák, Flora, additional, Held, Kathrin, additional, Lin, Luming, additional, Perkayvaz, Kami, additional, Leuning, Alexander, additional, Nicolai, Leo, additional, Pollakis, Georgios, additional, Buggert, Marcus, additional, Price, David A., additional, Rubio-Acero, Raquel, additional, Reich, Jakob, additional, Falk, Philine, additional, Markgraf, Alisa, additional, Puchinger, Kerstin, additional, Castellitti, Noemi, additional, Olbrich, Laura, additional, Vanshylla, Kanika, additional, Klein, Florian, additional, Wieser, Andreas, additional, Hasenauer, Jan, additional, Kroidl, Inge, additional, Hölscher, Michael, additional, and Geldmacher, Christof, additional

Published
2022
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19. SARS-CoV-2 Omicron sublineages exhibit distinct antibody escape patterns

Author

Gruell, Henning, primary, Vanshylla, Kanika, additional, Korenkov, Michael, additional, Tober-Lau, Pinkus, additional, Zehner, Matthias, additional, Münn, Friederike, additional, Janicki, Hanna, additional, Augustin, Max, additional, Schommers, Philipp, additional, Sander, Leif Erik, additional, Kurth, Florian, additional, Kreer, Christoph, additional, and Klein, Florian, additional

Published
2022
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20. Immunity after COVID-19 vaccination: protocol for a scoping review

Author

Kreuzberger, Nina, Hirsch, Caroline, Andreas, Marike, Böhm, Lena, Bröckelmann, Paul, Di Cristanziano, Veronica, Golinski, Martin, Kappler, Verena, Klein, Florian, Lange, Berit, Meerpohl, Joerg, Mikolajewska, Agata, Mörer, Onnen, Monsef, Ina, Park, Yun, Piechotta, Vanessa, Prinz, Carolin, Rodiah, Isti, Salomon, Susanne, Sander, Leif, Schmaderer, Christoph, Stegemann, Miriam, Stephani, Caspar, Vanshylla, Kanika, Weibel, Stephanie, and Skoetz, Nicole

Subjects
Virus Diseases, Medicine and Health Sciences, Medical Specialties, COVID-19, Infectious Disease, Diseases, scoping review, vaccines, immunity
Abstract

The objective of the planned scoping review is to provide an overview on the existing literature on immune response and long-term efficacy outcomes after COVID-19 vaccination, and to map this evidence according to the examined populations, specific vaccines, immunity parameters and their way of determining relevant long-term outcomes and the availability of mapping between immune reactivity and relevant outcomes. We will limit inclusion to literature on the four vaccines currently authorized by the EMA and vaccines authorized in at least 10 countries worldwide: • Comirnaty [Pfizer / Biontech], • Spikevax [Moderna], and its equivalent TAK-919 [Moderna formulation, Takeda] • Vaxzevria [Oxford / AstraZeneca] and its equivalent Covishield [Oxford / AstraZeneca formulation, Serum Institute of India] • COVID-19 Vaccine Janssen [Ad26.COV2.S] • Sputnik V [Gamaleya] • Sputnik Light [Gamaleya] • BBIBP-CorV (Vero Cells) [Sinopharm (Beijing)] • CoronaVac [Sinovac] (COVID-19 Vaccine (Vero Cell) Inactivated)

Published
2022
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21. Immunity after COVID-19 vaccination: a scoping review

Author

Kreuzberger, Nina, Hirsch, Caroline, Andreas, Marike, Böhm, Lena, Bröckelmann, Paul, Di Cristanziano, Veronica, Golinski, Martin, Kappler, Verena, Klein, Florian, Lange, Berit, Meerpohl, Joerg, Mikolajewska, Agata, Mörer, Onnen, Monsef, Ina, Park, Yun, Piechotta, Vanessa, Prinz, Carolin, Rodiah, Isti, Salomon, Susanne, Sander, Leif, Schmaderer, Christoph, Stegemann, Miriam, Stephani, Caspar, Vanshylla, Kanika, Weibel, Stephanie, and Skoetz, Nicole

Subjects
COVID-19, scoping review, vaccines, comorbidities
Abstract

The objective of the planned scoping review is to provide an overview on the existing literature on immune response and long-term efficacy outcomes after COVID-19 vaccination, and to map this evidence according to the examined populations, specific vaccines, immunity parameters and their way of determining relevant long-term outcomes and the availability of mapping between immune reactivity and relevant outcomes. We will limit inclusion to literature on the four vaccines currently authorized by the EMA and vaccines authorized in at least 10 countries worldwide: • Comirnaty [Pfizer / Biontech], • Spikevax [Moderna], and its equivalent TAK-919 [Moderna formulation, Takeda] • Vaxzevria [Oxford / AstraZeneca] and its equivalent Covishield [Oxford / AstraZeneca formulation, Serum Institute of India] • COVID-19 Vaccine Janssen [Ad26.COV2.S] • Sputnik V [Gamaleya] • Sputnik Light [Gamaleya] • BBIBP-CorV (Vero Cells) [Sinopharm (Beijing)] • CoronaVac [Sinovac] (COVID-19 Vaccine (Vero Cell) Inactivated)

Published
2022
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22. Immunity after COVID-19 vaccination in people with higher risk of compromised immune status: a scoping review

Author

Kreuzberger, Nina, additional, Hirsch, Caroline, additional, Andreas, Marike, additional, Böhm, Lena, additional, Bröckelmann, Paul J, additional, Di Cristanziano, Veronica, additional, Golinski, Martin, additional, Hausinger, Renate Ilona, additional, Mellinghoff, Sibylle, additional, Lange, Berit, additional, Lischetzki, Tina, additional, Kappler, Verena, additional, Mikolajewska, Agata, additional, Monsef, Ina, additional, Park, Yun Soo, additional, Piechotta, Vanessa, additional, Schmaderer, Christoph, additional, Stegemann, Miriam, additional, Vanshylla, Kanika, additional, Weber, Florencia, additional, Weibel, Stephanie, additional, Stephani, Caspar, additional, and Skoetz, Nicole, additional

Published
2022
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24. SARS-CoV-2 mRNA vaccinations fail to elicit humoral and cellular immune responses in patients with multiple sclerosis receiving fingolimod

Author

Meyer-Arndt, Lil, primary, Braun, Julian, additional, Fauchere, Florent, additional, Vanshylla, Kanika, additional, Loyal, Lucie, additional, Henze, Larissa, additional, Kruse, Beate, additional, Dingeldey, Manuela, additional, Jürchott, Karsten, additional, Mangold, Maike, additional, Maraj, Ardit, additional, Braginets, Andre, additional, Böttcher, Chotima, additional, Nitsche, Andreas, additional, de la Rosa, Kathrin, additional, Ratswohl, Christoph, additional, Sawitzki, Birgit, additional, Holenya, Pavlo, additional, Reimer, Ulf, additional, Sander, Leif E, additional, Klein, Florian, additional, Paul, Friedemann, additional, Bellmann-Strobl, Judith, additional, Thiel, Andreas, additional, and Giesecke-Thiel, Claudia, additional

Published
2022
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25. SARS-CoV-2-specific cellular response following third COVID-19 vaccination in patients with chronic lymphocytic leukemia

Author

Mellinghoff, Sibylle C., primary, Mayer, Leonie, additional, Robrecht, Sandra, additional, Weskamm, Leonie M., additional, Dahlke, Christine, additional, Gruell, Henning, additional, Schlotz, Maike, additional, Vanshylla, Kanika, additional, Schloser, Hans A., additional, Thelen, Martin, additional, Fink, Anna-Maria, additional, Fischer, Kirsten, additional, Klein, Florian, additional, Addo, Marylyn M., additional, Eichhorst, Barbara, additional, Hallek, Michael, additional, and Langerbeins, Petra, additional

Published
2022
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28. Design of an optimal combination therapy with broadly neutralizing antibodies to suppress HIV-1

Author

LaMont, Colin, Otwinowski, Jakub, Vanshylla, Kanika, Gruell, Henning, Klein, Florian, Nourmohammad, Armita, LaMont, Colin, Otwinowski, Jakub, Vanshylla, Kanika, Gruell, Henning, Klein, Florian, and Nourmohammad, Armita

Abstract

Infusion of broadly neutralizing antibodies (bNAbs) has shown promise as an alternative to anti-retroviral therapy against HIV. A key challenge is to suppress viral escape, which is more effectively achieved with a combination of bNAbs. Here, we propose a computational approach to predict the efficacy of a bNAb therapy based on the population genetics of HIV escape, which we parametrize using high-throughput HIV sequence data from bNAb-naive patients. By quantifying the mutational target size and the fitness cost of HIV-1 escape from bNAbs, we predict the distribution of rebound times in three clinical trials. We show that a cocktail of three bNAbs is necessary to effectively suppress viral escape, and predict the optimal composition of such bNAb cocktail. Our results offer a rational therapy design for HIV, and show how genetic data can be used to predict treatment outcomes and design new approaches to pathogenic control.

Published
2022

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

Author

Ercanoglu, Meryem Seda, Gieselmann, Lutz, Daehling, Sabrina, Poopalasingam, Nareshkumar, Detmer, Susanne, Koch, Manuel, Korenkov, Michael, Halwe, Sandro, Kluever, Michael, Di Cristanziano, Veronica, Janicki, Hanna, Schlotz, Maike, Worczinski, Johanna, Gathof, Birgit, Gruell, Henning, Zehner, Matthias, Becker, Stephan, Vanshylla, Kanika, Kreer, Christoph, Klein, Florian, Ercanoglu, Meryem Seda, Gieselmann, Lutz, Daehling, Sabrina, Poopalasingam, Nareshkumar, Detmer, Susanne, Koch, Manuel, Korenkov, Michael, Halwe, Sandro, Kluever, Michael, Di Cristanziano, Veronica, Janicki, Hanna, Schlotz, Maike, Worczinski, Johanna, Gathof, Birgit, Gruell, Henning, Zehner, Matthias, Becker, Stephan, Vanshylla, Kanika, Kreer, Christoph, and Klein, Florian

Abstract

Preexisting immunity against SARS-CoV-2 may have critical implications for our understanding of COVID-19 susceptibility and severity. The presence and clinical relevance of a preexisting B cell immunity remain to be fully elucidated. Here, we provide a detailed analysis of the B cell immunity to SARS-CoV-2 in unexposed individuals. To this end, we extensively investigated SARS-CoV-2 humoral immunity in 150 adults sampled pre-pandemically. Comprehensive screening of donor plasma and purified IgG sampler, for bin Jing and neutralization in various functional assays revealed no substantial activity against SARS-CoV-2 but broad reactivity to endemic betacoronaviruses. Moreover, we analyzed antibody sequences of 8,174 putatively SARS-CoV-2-reactive B cells at a single cell level and generated and tested 158 monoclonal antibodies. None of these antibodies displayed relevant binding or neutralizing activity against SARS-CoV-2. Taken together, our results show no evidence of competent preexisting antibody and B cell immunity against SARS-CoV-2 in unexposed adults.

Published
2022

30. Antibody-mediated neutralization of SARS-CoV-2

Author

Gruell, Henning, Vanshylla, Kanika, Weber, Timm, Barnes, Christopher O., Kreer, Christoph, Klein, Florian, Gruell, Henning, Vanshylla, Kanika, Weber, Timm, Barnes, Christopher O., Kreer, Christoph, and Klein, Florian

Abstract

Neutralizing antibodies can block infection, clear pathogens, and are essential to provide long-term immunity. Since the onset of the pandemic, SARS-CoV-2 neutralizing antibodies have been comprehensively investigated and critical information on their development, function, and potential use to prevent and treat COVID-19 have been revealed. With the emergence of SARS-CoV-2 immune escape variants, humoral immunity is being challenged, and a detailed understanding of neutralizing antibodies is essential to guide vaccine design strategies as well as antibody-mediated therapies. In this review, we summarize some of the key findings on SARS-CoV-2 neutralizing antibodies, with a focus on their clinical application.

Published
2022

31. SARS-CoV-2 mRNA vaccinations fail to elicit humoral and cellular immune responses in patients with multiple sclerosis receiving fingolimod

Author

Meyer-Arndt, Lil, Braun, Julian, Fauchere, Florent, Vanshylla, Kanika, Loyal, Lucie, Henze, Larissa, Kruse, Beate, Dingeldey, Manuela, Juerchott, Karsten, Mangold, Maike, Maraj, Ardit, Braginets, Andre, Boettcher, Chotima, Nitsche, Andreas, de la Rosa, Kathrin, Ratswohl, Christoph, Sawitzki, Birgit, Holenya, Pavlo, Reimer, Ulf, Sander, Leif E., Klein, Florian, Paul, Friedemann, Bellmann-Strobl, Judith, Thiel, Andreas, Giesecke-Thiel, Claudia, Meyer-Arndt, Lil, Braun, Julian, Fauchere, Florent, Vanshylla, Kanika, Loyal, Lucie, Henze, Larissa, Kruse, Beate, Dingeldey, Manuela, Juerchott, Karsten, Mangold, Maike, Maraj, Ardit, Braginets, Andre, Boettcher, Chotima, Nitsche, Andreas, de la Rosa, Kathrin, Ratswohl, Christoph, Sawitzki, Birgit, Holenya, Pavlo, Reimer, Ulf, Sander, Leif E., Klein, Florian, Paul, Friedemann, Bellmann-Strobl, Judith, Thiel, Andreas, and Giesecke-Thiel, Claudia

Abstract

Background SARS-CoV-2 mRNA vaccination of healthy individuals is highly immunogenic and protective against severe COVID-19. However, there are limited data on how disease-modifying therapies (DMTs) alter SARS-CoV-2 mRNA vaccine immunogenicity in patients with autoimmune diseases. Methods As part of a prospective cohort study, we investigated the induction, stability and boosting of vaccine-specific antibodies, B cells and T cells in patients with multiple sclerosis (MS) on different DMTs after homologous primary, secondary and booster SARS-CoV-2 mRNA vaccinations. Of 126 patients with MS analysed, 105 received either anti-CD20-based B cell depletion (aCD20-BCD), fingolimod, interferon-beta, dimethyl fumarate, glatiramer acetate, teriflunomide or natalizumab, and 21 were untreated MS patients for comparison. Results In contrast to all other MS patients, and even after booster, most aCD20-BCD- and fingolimod-treated patients showed no to markedly reduced anti-S1 IgG, serum neutralising activity and a lack of receptor binding domain-specific and S2-specific B cells. Patients receiving fingolimod additionally lacked spike-reactive CD4(+) T cell responses. The duration of fingolimod treatment, rather than peripheral blood B and T cell counts prior to vaccination, determined whether a humoral immune response was elicited. Conclusions The lack of immunogenicity under long-term fingolimod treatment demonstrates that functional immune responses require not only immune cells themselves, but also access of these cells to the site of inoculation and their unimpeded movement. The absence of humoral and T cell responses suggests that fingolimod-treated patients with MS are at risk for severe SARS-CoV-2 infections despite booster vaccinations, which is highly relevant for clinical decision-making and adapted protective measures, particularly considering additional recently approved sphingosine-1-phosphate receptor antagonists for MS treatment.

Published
2022

32. Immunity after COVID-19 vaccination in people with higher risk of compromised immune status: a scoping review

Author

Kreuzberger, Nina, Hirsch, Caroline, Andreas, Marike, Boehm, Lena, Broeckelmann, Paul J., Di Cristanziano, Veronica, Golinski, Martin, Hausinger, Renate Ilona, Mellinghoff, Sibylle, Lange, Berit, Lischetzki, Tina, Kappler, Verena, Mikolajewska, Agata, Monsef, Ina, Park, Yun Soo, Piechotta, Vanessa, Schmaderer, Christoph, Stegemann, Miriam, Vanshylla, Kanika, Weber, Florencia, Weibel, Stephanie, Stephani, Caspar, Skoetz, Nicole, Kreuzberger, Nina, Hirsch, Caroline, Andreas, Marike, Boehm, Lena, Broeckelmann, Paul J., Di Cristanziano, Veronica, Golinski, Martin, Hausinger, Renate Ilona, Mellinghoff, Sibylle, Lange, Berit, Lischetzki, Tina, Kappler, Verena, Mikolajewska, Agata, Monsef, Ina, Park, Yun Soo, Piechotta, Vanessa, Schmaderer, Christoph, Stegemann, Miriam, Vanshylla, Kanika, Weber, Florencia, Weibel, Stephanie, Stephani, Caspar, and Skoetz, Nicole

Abstract

Background High efficacy in terms of protection from severe COVID-19 has been demonstrated for several SARS-CoV-2 vaccines. However, patients with compromised immune status develop a weaker and less stable immune response to vaccination. Strong immune response may not always translate into clinical benefit, therefore it is important to synthesise evidence on modified schemes and types of vaccination in these population subgroups for guiding health decisions. As the literature on COVID-19 vaccines continues to expand, we aimed to scope the literature on multiple subgroups to subsequently decide on the most relevant research questions to be answered by systematic reviews. Objectives To provide an overview of the availability of existing literature on immune response and long-term clinical outcomes after COVID-19 vaccination, and to map this evidence according to the examined populations, specific vaccines, immunity parameters, and their way of determining relevant long-term outcomes and the availability of mapping between immune reactivity and relevant outcomes. Search methods We searched the Cochrane COVID-19 Study Register, the Web of Science Core Collection, and the World Health Organization COVID-19 Global literature on coronavirus disease on 6 December 2021. Selection criteria We included studies that published results on immunity outcomes after vaccination with BNT162b2, mRNA-1273, AZD1222, Ad26.COV2.S, Sputnik V or Sputnik Light, BBIBP-CorV, or CoronaVac on predefined vulnerable subgroups such as people with malignancies, transplant recipients, people undergoing renal replacement therapy, and people with immune disorders, as well as pregnant and breastfeeding women, and children. We included studies if they had at least 100 participants (not considering healthy control groups); we excluded case studies and case series. Data collection and analysis We extracted data independently and in duplicate onto an online data extraction form. Data were represented as tabl

Published
2022

33. Analysis of antibodies from HCV elite neutralizers identifies genetic determinants of broad neutralization

Author

Weber, Timm, Potthoff, Julian, Bizu, Sven, Labuhn, Maurice, Dold, Leona, Schoofs, Till, Horning, Marcel, Ercanoglu, Meryem S., Kreer, Christoph, Gieselmann, Lutz, Vanshylla, Kanika, Langhans, Bettina, Janicki, Hanna, Stroeh, Luisa J., Knops, Elena, Nierhoff, Dirk, Spengler, Ulrich, Kaiser, Rolf, Bjorkman, Pamela J., Krey, Thomas, Bankwitz, Dorothea, Pfeifer, Nico, Pietschmann, Thomas, Flyak, Andrew, I, Klein, Florian, Weber, Timm, Potthoff, Julian, Bizu, Sven, Labuhn, Maurice, Dold, Leona, Schoofs, Till, Horning, Marcel, Ercanoglu, Meryem S., Kreer, Christoph, Gieselmann, Lutz, Vanshylla, Kanika, Langhans, Bettina, Janicki, Hanna, Stroeh, Luisa J., Knops, Elena, Nierhoff, Dirk, Spengler, Ulrich, Kaiser, Rolf, Bjorkman, Pamela J., Krey, Thomas, Bankwitz, Dorothea, Pfeifer, Nico, Pietschmann, Thomas, Flyak, Andrew, I, and Klein, Florian

Abstract

The high genetic diversity of hepatitis C virus (HCV) complicates effective vaccine development. We screened a cohort of 435 HCV-infected individuals and found that 2%-5% demonstrated outstanding HCV-neutralizing activity. From four of these patients, we isolated 310 HCV antibodies, including neutralizing antibodies with exceptional breadth and potency. High neutralizing activity was enabled by the use of the VH1-69 heavy chain gene segment, somatic mutations within CDRH1, and CDRH2 hydrophobicity. Structural and mutational analyses revealed an important role for mutations replacing the serines at positions 30 and 31, as well as the presence of neutral and hydrophobic residues at the tip of the CDRH3. Based on these characteristics, we computationally created a de novo antibody with a fully synthetic VH1-69 heavy chain that efficiently neutralized multiple HCV genotypes. Our findings provide a deep understanding of the generation of broadly HCV-neutralizing antibodies that can guide the design of effective vaccine candidates.

Published
2022

34. Durability of omicron-neutralising serum activity after mRNA booster immunisation in older adults

Author

Vanshylla, Kanika, Tober-Lau, Pinkus, Gruell, Henning, Muenn, Friederike, Eggeling, Ralf, Pfeifer, Nico, Le, N. Han, Landgraf, Irmgard, Kurth, Florian, Sander, Leif E., Klein, Florian, Vanshylla, Kanika, Tober-Lau, Pinkus, Gruell, Henning, Muenn, Friederike, Eggeling, Ralf, Pfeifer, Nico, Le, N. Han, Landgraf, Irmgard, Kurth, Florian, Sander, Leif E., and Klein, Florian

Published
2022

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

Author

Vanshylla, Kanika, Fan, Chengcheng, Wunsch, Marie, Poopalasingam, Nareshkumar, Meijers, Matthijs, Kreer, Christoph, Kleipass, Franziska, Ruchnewitz, Denis, Ercanoglu, Meryem S., Gruell, Henning, Muenn, Friederike, Pohl, Kai, Janicki, Hanna, Nolden, Tobias, Bartl, Simone, Stein, Saskia C., Augustin, Max, Dewald, Felix, Gieselmann, Lutz, Schommers, Philipp, Schulz, Thomas F., Sander, Leif Erik, Koch, Manuel, Luksza, Marta, Laessig, Michael, Bjorkman, Pamela J., Klein, Florian, Vanshylla, Kanika, Fan, Chengcheng, Wunsch, Marie, Poopalasingam, Nareshkumar, Meijers, Matthijs, Kreer, Christoph, Kleipass, Franziska, Ruchnewitz, Denis, Ercanoglu, Meryem S., Gruell, Henning, Muenn, Friederike, Pohl, Kai, Janicki, Hanna, Nolden, Tobias, Bartl, Simone, Stein, Saskia C., Augustin, Max, Dewald, Felix, Gieselmann, Lutz, Schommers, Philipp, Schulz, Thomas F., Sander, Leif Erik, Koch, Manuel, Luksza, Marta, Laessig, Michael, Bjorkman, Pamela J., and Klein, Florian

Abstract

A fraction of COVID-19 convalescent individuals mount a potent antibody response to SARS-CoV-2 with cross-reactivity to SARS-CoV-1. To uncover their humoral response in detail, we performed single B cell analysis from 10 SARS-CoV-2 elite neutralizers. We isolated and analyzed 126 monoclonal antibodies, many of which were sarbecovirus cross-reactive, with some displaying merbecovirus-and embecovirus-reactivity. Several isolated broadly neutralizing antibodies were effective against B.1.1.7, B.1.351, B.1.429, B.1.617, and B.1.617.2 variants and 19 prominent potential escape sites. Furthermore, assembly of 716,806 SARSCoV-2 sequences predicted emerging escape variants, which were also effectively neutralized. One of these broadly neutralizing potent antibodies, R40-1G8, is a IGHV3-53 RBD-class-1 antibody. Remarkably, cryo-EM analysis revealed that R40-1G8 has a flexible binding mode, targeting both upand downconformations of the RBD. Given the threat of emerging SARS-CoV-2 variants, we demonstrate that elite neutralizers are a valuable source for isolating ultrapotent antibody candidates to prevent and treat SARS-CoV-2 infection.

Published
2022

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

Author

Gruell, Henning, Vanshylla, Kanika, Korenkov, Michael, Tober-Lau, Pinkus, Zehner, Matthias, Munn, Friederike, Janicki, Hanna, Augustin, Max, Schommers, Philipp, Sander, Leif Erik, Kurth, Florian, Kreer, Christoph, Klein, Florian, Gruell, Henning, Vanshylla, Kanika, Korenkov, Michael, Tober-Lau, Pinkus, Zehner, Matthias, Munn, Friederike, Janicki, Hanna, Augustin, Max, Schommers, Philipp, Sander, Leif Erik, Kurth, Florian, Kreer, Christoph, and Klein, Florian

Abstract

SARS-CoV-2 neutralizing antibodies play a critical role in COVID-19 prevention and treatment but are challenged by viral evolution and the emergence of novel escape variants. Importantly, the recently identified Omicron sublineages BA.2.12.1 and BA.4/5 are rapidly becoming predominant in various countries. By deter-mining polyclonal serum activity of 50 convalescent or vaccinated individuals against BA.1, BA.1.1, BA.2, BA.2.12.1, and BA.4/5, we reveal a further reduction in BA.4/5 susceptibility to vaccinee sera. Most notably, delineation of sensitivity to an extended 163-antibody panel demonstrates pronounced antigenic differences with distinct escape patterns among Omicron sublineages. Antigenic distance and/or higher resistance may therefore favor immune-escape-mediated BA.4/5 expansion after the first Omicron wave. Finally, while most clinical-stage monoclonal antibodies are inactive against Omicron sublineages, we identify promising antibodies with high pan-SARS-CoV-2 neutralizing potency. Our study provides a detailed understanding of Omicron-sublineage antibody escape that can inform on effective strategies against COVID-19.

Published
2022

37. SARS-CoV-2-specific cellular response following third COVID-19 vaccination in patients with chronic lymphocytic leukemia

Author

Mellinghoff, Sibylle C., Mayer, Leonie, Robrecht, Sandra, Weskamm, Leonie M., Dahlke, Christine, Gruell, Henning, Schlotz, Maike, Vanshylla, Kanika, Schloesser, Hans A., Thelen, Martin, Fink, AnnaMaria, Fischer, Kirsten, Klein, Florian, Addo, Marylyn M., Eichhorst, Barbara, Hallek, Michael, Langerbeins, Petra, Mellinghoff, Sibylle C., Mayer, Leonie, Robrecht, Sandra, Weskamm, Leonie M., Dahlke, Christine, Gruell, Henning, Schlotz, Maike, Vanshylla, Kanika, Schloesser, Hans A., Thelen, Martin, Fink, AnnaMaria, Fischer, Kirsten, Klein, Florian, Addo, Marylyn M., Eichhorst, Barbara, Hallek, Michael, and Langerbeins, Petra

Published
2022

38. Delineating antibody escape from Omicron sublineages

Author

Gruell, Henning, primary, Vanshylla, Kanika, additional, Korenkov, Michael, additional, Tober-Lau, Pinkus, additional, Zehner, Matthias, additional, Münn, Friederike, additional, Janicki, Hanna, additional, Augustin, Max, additional, Schommers, Philipp, additional, Sander, Leif Erik, additional, Kurth, Florian, additional, Kreer, Christoph, additional, and Klein, Florian, additional

Published
2022
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40. No substantial preexisting B cell immunity against SARS-CoV-2 in healthy adults

Author

Ercanoglu, Meryem Seda, primary, Gieselmann, Lutz, additional, Dähling, Sabrina, additional, Poopalasingam, Nareshkumar, additional, Detmer, Susanne, additional, Koch, Manuel, additional, Korenkov, Michael, additional, Halwe, Sandro, additional, Klüver, Michael, additional, Di Cristanziano, Veronica, additional, Janicki, Hanna, additional, Schlotz, Maike, additional, Worczinski, Johanna, additional, Gathof, Birgit, additional, Gruell, Henning, additional, Zehner, Matthias, additional, Becker, Stephan, additional, Vanshylla, Kanika, additional, Kreer, Christoph, additional, and Klein, Florian, additional

Published
2022
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41. SARS-CoV-2 mRNA vaccination fails to elicit humoral and cellular immune responses in multiple sclerosis patients receiving fingolimod

Author

Meyer-Arndt, Lil, primary, Braun, Julian, additional, Fauchere, Florent, additional, Vanshylla, Kanika, additional, Loyal, Lucie, additional, Henze, Larissa, additional, Kruse, Beate, additional, Dingeldey, Manuela, additional, Juerchott, Karsten, additional, Mangold, Maike, additional, Maraj, Ardit, additional, Braginets, Andre, additional, Boettcher, Chotima, additional, Nitsche, Andreas, additional, de la Rosa, Kathrin, additional, Ratswohl, Christoph, additional, Sawitzki, Birgit, additional, Holenya, Pavlo, additional, Reimer, Ulf, additional, Sander, Leif Erik, additional, Klein, Florian, additional, Paul, Friedemann, additional, Bellmann-Strobl, Judith, additional, Thiel, Andreas, additional, and Giesecke-Thiel, Claudia, additional

Published
2022
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43. Analysis of antibodies from HCV elite neutralizers identifies genetic determinants of broad neutralization

Author

Weber, Timm, primary, Potthoff, Julian, additional, Bizu, Sven, additional, Labuhn, Maurice, additional, Dold, Leona, additional, Schoofs, Till, additional, Horning, Marcel, additional, Ercanoglu, Meryem S., additional, Kreer, Christoph, additional, Gieselmann, Lutz, additional, Vanshylla, Kanika, additional, Langhans, Bettina, additional, Janicki, Hanna, additional, Ströh, Luisa J., additional, Knops, Elena, additional, Nierhoff, Dirk, additional, Spengler, Ulrich, additional, Kaiser, Rolf, additional, Bjorkman, Pamela J., additional, Krey, Thomas, additional, Bankwitz, Dorothea, additional, Pfeifer, Nico, additional, Pietschmann, Thomas, additional, Flyak, Andrew I., additional, and Klein, Florian, additional

Published
2022
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44. Discovery of ultrapotent broadly neutralizing antibodies from SARS-CoV-2 elite neutralizers

Author

Vanshylla, Kanika, primary, Fan, Chengcheng, additional, Wunsch, Marie, additional, Poopalasingam, Nareshkumar, additional, Meijers, Matthijs, additional, Kreer, Christoph, additional, Kleipass, Franziska, additional, Ruchnewitz, Denis, additional, Ercanoglu, Meryem S., additional, Gruell, Henning, additional, Münn, Friederike, additional, Pohl, Kai, additional, Janicki, Hanna, additional, Nolden, Tobias, additional, Bartl, Simone, additional, Stein, Saskia C., additional, Augustin, Max, additional, Dewald, Felix, additional, Gieselmann, Lutz, additional, Schommers, Philipp, additional, Schulz, Thomas F., additional, Sander, Leif Erik, additional, Koch, Manuel, additional, Łuksza, Marta, additional, Lässig, Michael, additional, Bjorkman, Pamela J., additional, and Klein, Florian, additional

Published
2022
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46. SARS-CoV-2 specific cellular response following COVID-19 vaccination in patients with chronic lymphocytic leukemia

Author

Mellinghoff, Sibylle C., primary, Robrecht, Sandra, additional, Mayer, Leonie, additional, Weskamm, Leonie M., additional, Dahlke, Christine, additional, Gruell, Henning, additional, Vanshylla, Kanika, additional, Schlösser, Hans A., additional, Thelen, Martin, additional, Fink, Anna-Maria, additional, Fischer, Kirsten, additional, Klein, Florian, additional, Addo, Marylyn M., additional, Eichhorst, Barbara, additional, Hallek, Michael, additional, and Langerbeins, Petra, additional

Published
2021
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47. Case Report: Clinical Management of a Patient With Metastatic Non-Small Cell Lung Cancer Newly Receiving Immune Checkpoint Inhibition During Symptomatic COVID-19

Author

Mellinghoff, Sibylle C., primary, Vanshylla, Kanika, additional, Dahlke, Christine, additional, Addo, Marylyn M., additional, Cornely, Oliver A., additional, Klein, Florian, additional, Persigehl, Thorsten, additional, Rybniker, Jan, additional, Gruell, Henning, additional, and Bröckelmann, Paul J., additional

Published
2021
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49. Safety, reactogenicity, and immunogenicity of homologous and heterologous prime-boost immunisation with ChAdOx1 nCoV-19 and BNT162b2: a prospective cohort study

Author

Hillus, David, primary, Schwarz, Tatjana, additional, Tober-Lau, Pinkus, additional, Vanshylla, Kanika, additional, Hastor, Hana, additional, Thibeault, Charlotte, additional, Jentzsch, Stefanie, additional, Helbig, Elisa T, additional, Lippert, Lena J, additional, Tscheak, Patricia, additional, Schmidt, Marie Luisa, additional, Riege, Johanna, additional, Solarek, André, additional, von Kalle, Christof, additional, Dang-Heine, Chantip, additional, Gruell, Henning, additional, Kopankiewicz, Piotr, additional, Suttorp, Norbert, additional, Drosten, Christian, additional, Bias, Harald, additional, Seybold, Joachim, additional, Klein, Florian, additional, Kurth, Florian, additional, Corman, Victor Max, additional, Sander, Leif Erik, additional, Al-Rim, Ben, additional, Bardtke, Lara, additional, Beheim-Schwarzbach, Jörn Ilmo, additional, Behn, Kerstin, additional, Bergfeld, Leon, additional, Bethke, Norma, additional, Bleicker, Tobias, additional, Briesemeister, Dana, additional, Brumhard, Sophia, additional, Conrad, Claudia, additional, Dieckmann, Sebastian, additional, Frey, Doris, additional, Gabelich, Julie-Anne, additional, Georg, Philipp, additional, Gläser, Ute, additional, Hasler, Lisbeth, additional, Hetey, Andreas, additional, Hiller, Anna Luisa, additional, Horn, Alexandra, additional, Hülso, Claudia, additional, Kegel, Luisa, additional, Koch, Willi, additional, Krannich, Alexander, additional, Kroneberg, Paolo, additional, Lisy, Michelle, additional, Mackeldanz, Petra, additional, Maeß, Birgit, additional, Münn, Friederike, additional, Olk, Nadine, additional, Peiser, Christian, additional, Pohl, Kai, additional, Hermel, Annelie, additional, Rönnefarth, Maria, additional, Rubisch, Carolin, additional, Sanchez Rezza, Angela, additional, Schellenberger, Isabelle, additional, Schenkel, Viktoria, additional, Schlesinger, Jenny, additional, Schmidt, Sein, additional, Schwanitz, Georg, additional, Sinnigen, Anne-Sophie, additional, Stubbemann, Paula, additional, Tesch, Julia, additional, Treue, Denise, additional, Wendisch, Daniel, additional, and Zvorc, Saskia, additional

Published
2021
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50. Long-term immunogenicity of BNT162b2 vaccination in older people and younger health-care workers

Author

Tober-Lau, Pinkus, primary, Schwarz, Tatjana, additional, Vanshylla, Kanika, additional, Hillus, David, additional, Gruell, Henning, additional, Suttorp, Norbert, additional, Landgraf, Irmgard, additional, Kappert, Kai, additional, Seybold, Joachim, additional, Drosten, Christian, additional, Klein, Florian, additional, Kurth, Florian, additional, Sander, Leif Erik, additional, and Corman, Victor Max, additional

Published
2021
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