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2. Understanding repertoire sequencing data through a multiscale computational model of the germinal center

Author

García-Valiente, Rodrigo, Merino Tejero, Elena, Stratigopoulou, Maria, Balashova, Daria, Jongejan, Aldo, Lashgari, Danial, Pélissier, Aurélien, Caniels, Tom G., Claireaux, Mathieu A. F., Musters, Anne, van Gils, Marit J., Rodríguez Martínez, María, de Vries, Niek, Meyer-Hermann, Michael, Guikema, Jeroen E. J., Hoefsloot, Huub, and van Kampen, Antoine H. C.

Published
2023
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3. Broad SARS-CoV-2 neutralization by monoclonal and bispecific antibodies derived from a Gamma-infected individual

Author

Guerra, Denise, Beaumont, Tim, Radić, Laura, Kerster, Gius, van der Straten, Karlijn, Yuan, Meng, Torres, Jonathan L., Lee, Wen-Hsin, Liu, Hejun, Poniman, Meliawati, Bontjer, Ilja, Burger, Judith A., Claireaux, Mathieu, Caniels, Tom G., Snitselaar, Jonne L., Bijl, Tom P.L., Kruijer, Sabine, Ozorowski, Gabriel, Gideonse, David, Sliepen, Kwinten, Ward, Andrew B., Eggink, Dirk, de Bree, Godelieve J., Wilson, Ian A., Sanders, Rogier W., and van Gils, Marit J.

Published
2023
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4. Germline-targeting HIV-1 Env vaccination induces VRC01-class antibodies with rare insertions

Author

Caniels, Tom G., Medina-Ramírez, Max, Zhang, Jinsong, Sarkar, Anita, Kumar, Sonu, LaBranche, Alex, Derking, Ronald, Allen, Joel D., Snitselaar, Jonne L., Capella-Pujol, Joan, Sánchez, Iván del Moral, Yasmeen, Anila, Diaz, Marilyn, Aldon, Yoann, Bijl, Tom P.L., Venkatayogi, Sravani, Martin Beem, Joshua S., Newman, Amanda, Jiang, Chuancang, Lee, Wen-Hsin, Pater, Maarten, Burger, Judith A., van Breemen, Mariëlle J., de Taeye, Steven W., Rantalainen, Kimmo, LaBranche, Celia, Saunders, Kevin O., Montefiori, David, Ozorowski, Gabriel, Ward, Andrew B., Crispin, Max, Moore, John P., Klasse, Per Johan, Haynes, Barton F., Wilson, Ian A., Wiehe, Kevin, Verkoczy, Laurent, and Sanders, Rogier W.

Published
2023
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5. Co-display of diverse spike proteins on nanoparticles broadens sarbecovirus neutralizing antibody responses

Author

Brinkkemper, Mitch, Veth, Tim S., Brouwer, Philip J.M., Turner, Hannah, Poniman, Meliawati, Burger, Judith A., Bouhuijs, Joey H., Olijhoek, Wouter, Bontjer, Ilja, Snitselaar, Jonne L., Caniels, Tom G., van der Linden, Cynthia A., Ravichandran, Rashmi, Villaudy, Julien, van der Velden, Yme U., Sliepen, Kwinten, van Gils, Marit J., Ward, Andrew B., King, Neil P., Heck, Albert J.R., and Sanders, Rogier W.

Published
2022
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7. A public antibody class recognizes an S2 epitope exposed on open conformations of SARS-CoV-2 spike

Author

Claireaux, Mathieu, Caniels, Tom G., de Gast, Marlon, Han, Julianna, Guerra, Denise, Kerster, Gius, van Schaik, Barbera D. C., Jongejan, Aldo, Schriek, Angela I., Grobben, Marloes, Brouwer, Philip J. M., van der Straten, Karlijn, Aldon, Yoann, Capella-Pujol, Joan, Snitselaar, Jonne L., Olijhoek, Wouter, Aartse, Aafke, Brinkkemper, Mitch, Bontjer, Ilja, Burger, Judith A., Poniman, Meliawati, Bijl, Tom P. L., Torres, Jonathan L., Copps, Jeffrey, Martin, Isabel Cuella, de Taeye, Steven W., de Bree, Godelieve J., Ward, Andrew B., Sliepen, Kwinten, van Kampen, Antoine H. C., Moerland, Perry D., Sanders, Rogier W., and van Gils, Marit J.

Published
2022
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9. A single mRNA vaccine dose in COVID-19 patients boosts neutralizing antibodies against SARS-CoV-2 and variants of concern

Author

Agard, Ivette, Ayal, Jane, Boyd, Anders, Cavdar, Floor, Craanen, Marianne, Davidovich, Udi, Deuring, Annemarieke, van Dijk, Annelies, Ersan, Ertan, del Grande, Laura, Hartman, Joost, Koedoot, Nelleke, Leenstra, Tjalling, Loomans, Dominique, Makowska, Agata, du Maine, Tom, de Man, Ilja, Matser, Amy, van der Meij, Lizenka, van Polanen, Marleen, Oud, Maria, Reid, Clark, Storey, Leeann, de Wit, Marije, van Wijk, Marc, van Assem, Joyce, van den Aardweg, Joost, van Beek, Marijne, Blankert, Thyra, Boeser-Nunnink, Brigitte, Moll van Charante, Eric, van Dort, Karel, Figaroa, Orlane, Frenkel, Leah, Girigorie, Arginell, van Haga, Jelle, Harskamp-Holwerda, Agnes, Hazenberg, Mette, Hidad, Soemeja, de Jong, Nina, Jonges, Marcel, Jurriaans, Suzanne, Knoop, Hans, Kuijt, Lara, Lok, Anja, Ruiz, Marga Mangas, Maurer, Irma, Nieuwkerk, Pythia, van Nuenen, Ad, van der Veen, Annelou, Verkaik, Bas, Visser, Gerben-Rienk, van Gils, Marit J., van Willigen, Hugo D.G., Wynberg, Elke, Han, Alvin X., van der Straten, Karlijn, Burger, Judith A., Poniman, Meliawati, Oomen, Melissa, Tejjani, Khadija, Bouhuijs, Joey H., Verveen, Anouk, Lebbink, Romy, Dijkstra, Maartje, Appelman, Brent, Lavell, A.H. Ayesha, Caniels, Tom G., Bontjer, Ilja, van Vught, Lonneke A., Vlaar, Alexander P.J., Sikkens, Jonne J., Bomers, Marije K., Russell, Colin A., Kootstra, Neeltje A., Sanders, Rogier W., Prins, Maria, de Bree, Godelieve J., and de Jong, Menno D.

Published
2022
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10. Germline-targeting HIV vaccination induces neutralizing antibodies to the CD4 binding site.

Author

Caniels, Tom G., Medina-Ramìrez, Max, Zhang, Shiyu, Kratochvil, Sven, Xian, Yuejiao, Koo, Ja-Hyun, Derking, Ronald, Samsel, Jakob, van Schooten, Jelle, Pecetta, Simone, Lamperti, Edward, Yuan, Meng, Carrasco, María Ríos, del Moral Sánchez, Iván, Allen, Joel D., Bouhuijs, Joey H., Yasmeen, Anila, Ketas, Thomas J., Snitselaar, Jonne L., and Bijl, Tom P. L.

Subjects
AIDS vaccines, BINDING sites, B cells, VACCINE development, IMMUNOGLOBULINS
Abstract

Eliciting potent and broadly neutralizing antibodies (bnAbs) is a major goal in HIV-1 vaccine development. Here, we describe how germline-targeting immunogen BG505 SOSIP germline trimer 1.1 (GT1.1), generated through structure-based design, engages a diverse range of VRC01-class bnAb precursors. A single immunization with GT1.1 expands CD4 binding site (CD4bs)–specific VRC01-class B cells in knock-in mice and drives VRC01-class maturation. In nonhuman primates (NHPs), GT1.1 primes CD4bs-specific neutralizing serum responses. Selected monoclonal antibodies (mAbs) isolated from GT1.1-immunized NHPs neutralize fully glycosylated BG505 virus. Two mAbs, 12C11 and 21N13, neutralize subsets of diverse heterologous neutralization-resistant viruses. High-resolution structures revealed that 21N13 targets the same conserved residues in the CD4bs as VRC01-class and CH235-class bnAbs despite its low sequence similarity (~40%), whereas mAb 12C11 binds predominantly through its heavy chain complementarity-determining region 3. These preclinical data underpin the ongoing evaluation of GT1.1 in a phase 1 clinical trial in healthy volunteers. Editor's summary: HIV vaccine efforts include developing immunogens that induce broadly neutralizing antibodies (bnAbs). Two studies highlight advances in inducing VRC01-class bnAbs that bind to the conserved CD4 binding site (CD4bs) epitope of the HIV envelope (Env). Caniels et al. used structure-based design to optimize a trimeric HIV Env antigen called BG505 SOSIP GT1.1 (GT1.1). Adult nonhuman primates (NHPs) immunized with GT1.1 produced antibodies that neutralized fully glycosylated viruses by specifically binding to the CD4bs. Nelson et al. evaluated GT1.1 in infant NHPs compared with a predecessor immunogen, BG505 SOSIP. Both immunogens induced neutralizing antibodies against autologous viruses, but only infants primed with GT1.1 generated VRC01-like CD4bs bnAb precursors upon boosting with BG505 SOSIP. These findings indicate that trimeric germline-targeting immunogens can elicit neutralizing antibodies toward conserved HIV Env epitopes. (See accompanying Research Article by Nelson et al. and accompanying Focus by Amara.) —Christiana Fogg [ABSTRACT FROM AUTHOR]

Published
2024
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11. COVA1-18 neutralizing antibody protects against SARS-CoV-2 in three preclinical models

Author

Maisonnasse, Pauline, Aldon, Yoann, Marc, Aurélien, Marlin, Romain, Dereuddre-Bosquet, Nathalie, Kuzmina, Natalia A., Freyn, Alec W., Snitselaar, Jonne L., Gonçalves, Antonio, Caniels, Tom G., Burger, Judith A., Poniman, Meliawati, Bontjer, Ilja, Chesnais, Virginie, Diry, Ségolène, Iershov, Anton, Ronk, Adam J., Jangra, Sonia, Rathnasinghe, Raveen, Brouwer, Philip J. M., Bijl, Tom P. L., van Schooten, Jelle, Brinkkemper, Mitch, Liu, Hejun, Yuan, Meng, Mire, Chad E., van Breemen, Mariëlle J., Contreras, Vanessa, Naninck, Thibaut, Lemaître, Julien, Kahlaoui, Nidhal, Relouzat, Francis, Chapon, Catherine, Ho Tsong Fang, Raphaël, McDanal, Charlene, Osei-Twum, Mary, St-Amant, Natalie, Gagnon, Luc, Montefiori, David C., Wilson, Ian A., Ginoux, Eric, de Bree, Godelieve J., García-Sastre, Adolfo, Schotsaert, Michael, Coughlan, Lynda, Bukreyev, Alexander, van der Werf, Sylvie, Guedj, Jérémie, Sanders, Rogier W., van Gils, Marit J., and Le Grand, Roger

Published
2021
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13. Antibody responses against SARS-CoV-2 variants induced by four different SARS-CoV-2 vaccines in health care workers in the Netherlands: A prospective cohort study

Author

van Gils, Marit J., Lavell, Ayesha, van der Straten, Karlijn, Appelman, Brent, Bontjer, Ilja, Poniman, Meliawati, Burger, Judith A., Oomen, Melissa, Bouhuijs, Joey H., van Vught, Lonneke A., Slim, Marleen A., Schinkel, Michiel, Wynberg, Elke, van Willigen, Hugo D. G., Grobben, Marloes, Tejjani, Khadija, van Rijswijk, Jacqueline, Snitselaar, Jonne L., Caniels, Tom G., Vlaar, Alexander P. J., Prins, Maria, de Jong, Menno D., de Bree, Godelieve J., Sikkens, Jonne J., Bomers, Marije K., and Sanders, Rogier W.

Subjects
Viral antibodies -- Evaluation -- Comparative analysis, Antibodies -- Evaluation -- Comparative analysis, Medical personnel -- Health aspects, Biological sciences
Abstract

Background Emerging and future SARS-CoV-2 variants may jeopardize the effectiveness of vaccination campaigns. Therefore, it is important to know how the different vaccines perform against diverse SARS-CoV-2 variants. Methods and findings In a prospective cohort of 165 SARS-CoV-2 naive health care workers in the Netherlands, vaccinated with either one of four vaccines (BNT162b2, mRNA-1273, AZD1222 or Ad26.COV2.S), we performed a head-to-head comparison of the ability of sera to recognize and neutralize SARS-CoV-2 variants of concern (VOCs; Alpha, Beta, Gamma, Delta and Omicron). Repeated serum sampling was performed 5 times during a year (from January 2021 till January 2022), including before and after booster vaccination with BNT162b2. Four weeks after completing the initial vaccination series, SARS-CoV-2 wild-type neutralizing antibody titers were highest in recipients of mRNA-1273, followed by recipients of BNT162b2 (geometric mean titers (GMT) of 358 [95% CI 231-556] and 214 [95% CI 153-299], respectively; p Conclusions Overall, this study shows that the mRNA vaccines appear superior to adenovirus vector-based vaccines in inducing neutralizing antibodies against VOCs four weeks after initial vaccination and after booster vaccination, which implies the use of mRNA vaccines for both initial and booster vaccination., Author(s): Marit J. van Gils 1,*, Ayesha Lavell 2, Karlijn van der Straten 1,3, Brent Appelman 4, Ilja Bontjer 1, Meliawati Poniman 1, Judith A. Burger 1, Melissa Oomen 1, [...]

Published
2022
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14. SARS-CoV-2 Spike N-Terminal Domain Engages 9-O-Acetylated α2–8-Linked Sialic Acids

Author

Tomris, Ilhan, primary, Unione, Luca, additional, Nguyen, Linh, additional, Zaree, Pouya, additional, Bouwman, Kim M., additional, Liu, Lin, additional, Li, Zeshi, additional, Fok, Jelle A., additional, Ríos Carrasco, María, additional, van der Woude, Roosmarijn, additional, Kimpel, Anne L. M., additional, Linthorst, Mirte W., additional, Kilavuzoglu, Sinan E., additional, Verpalen, Enrico C. J. M., additional, Caniels, Tom G., additional, Sanders, Rogier W., additional, Heesters, Balthasar A., additional, Pieters, Roland J., additional, Jiménez-Barbero, Jesús, additional, Klassen, John S., additional, Boons, Geert-Jan, additional, and de Vries, Robert P., additional

Published
2023
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15. Identification of New Drugs to Counteract Anti-Spike IgG-Induced Hyperinflammation in Severe COVID-19

Author

Geyer, Chiara E., primary, Chen, Hung-Jen, additional, Bye, Alexander P., additional, Manz, Xue D., additional, Guerra, Denise, additional, Caniels, Tom G., additional, Bijl, Tom PL, additional, Griffith, Guillermo R., additional, Hoepel, Willianne, additional, de Taeye, Steven W., additional, Veth, Jennifer, additional, Vlaar, Alexander P. J., additional, anon, Amsterdam, additional, Vidarsson, Gestur, additional, Bogaard, Harm Jan, additional, Aman, Jurjan, additional, Gibbins, Jonathan M., additional, van Gils, Marit J., additional, de Winther, Menno, additional, and den Dunnen, Jeroen, additional

Published
2023
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16. Broad SARS-CoV-2 Neutralization by Monoclonal and Bispecific Antibodies Derived from a Gamma-infected Individual

Author

Guerra, Denise, primary, Beaumont, Tim, additional, Radić, Laura, additional, Kerster, Gius, additional, van der Straten, Karlijn, additional, Yuan, Meng, additional, Torres, Jonathan L., additional, Lee, Wen-Hsin, additional, Liu, Hejun, additional, Poniman, Meliawati, additional, Bontjer, Ilja, additional, Burger, Judith A., additional, Claireaux, Mathieu, additional, Caniels, Tom G., additional, Snitselaar, Jonne L., additional, Bijl, Tom P. L., additional, Kruijer, Sabine, additional, Ozorowski, Gabriel, additional, Gideonse, David, additional, Sliepen, Kwinten, additional, Ward, Andrew B., additional, Eggink, Dirk, additional, de Bree, Godelieve J., additional, Wilson, Ian A., additional, Sanders, Rogier W., additional, and van Gils, Marit J., additional

Published
2022
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17. The SARS-CoV-2 spike N-terminal domain engages 9-O-acetylated α2-8-linked sialic acids

Author

Tomris, Ilhan, primary, Unione, Luca, additional, Nguyen, Linh, additional, Zaree, Pouya, additional, Bouwman, Kim M., additional, Liu, Lin, additional, Li, Zeshi, additional, Fok, Jelle A., additional, Ríos Carrasco, María, additional, van der Woude, Roosmarijn, additional, Kimpel, Anne L.M., additional, Linthorst, Mirte W., additional, Verpalen, Enrico C.J.M, additional, Caniels, Tom G., additional, Sanders, Rogier W., additional, Heesters, Balthasar A., additional, Pieters, Roland J., additional, Jiménez-Barbero, Jesús, additional, Klassen, John S., additional, Boons, Geert-Jan, additional, and de Vries, Robert P., additional

Published
2022
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18. Antigenic cartography using sera from sequence-confirmed SARS-CoV-2 variants of concern infections reveals antigenic divergence of Omicron

Author

van der Straten, Karlijn, primary, Guerra, Denise, additional, van Gils, Marit J., additional, Bontjer, Ilja, additional, Caniels, Tom G., additional, van Willigen, Hugo D.G., additional, Wynberg, Elke, additional, Poniman, Meliawati, additional, Burger, Judith A., additional, Bouhuijs, Joey H., additional, van Rijswijk, Jacqueline, additional, Olijhoek, Wouter, additional, Liesdek, Marinus H., additional, Lavell, A.H. Ayesha, additional, Appelman, Brent, additional, Sikkens, Jonne J., additional, Bomers, Marije K., additional, Han, Alvin X., additional, Nichols, Brooke E., additional, Prins, Maria, additional, Vennema, Harry, additional, Reusken, Chantal, additional, de Jong, Menno D., additional, de Bree, Godelieve J., additional, Russell, Colin A., additional, Eggink, Dirk, additional, and Sanders, Rogier W., additional

Published
2022
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19. Understanding repertoire sequencing data through a multiscale computational model of the germinal center

Author

Kampen, Antoine H. C. van, primary, García-Valiente, Rodrigo, additional, Tejero, Elena Merino, additional, Stratigopoulou, Maria, additional, Balashova, Daria, additional, Jongejan, Aldo, additional, Lashgari, Danial, additional, Pélissier, Aurélien, additional, Caniels, Tom G., additional, Claireaux, Mathieu A. F., additional, Musters, Anne, additional, Gils, Marit J. van, additional, Martinez, Maria Rodriguez, additional, de Vries, Niek, additional, Meyer-Hermann, Michael, additional, Guikema, Jeroen E.J., additional, and Hoefsloot, Huub, additional

Published
2022
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20. Discriminating cross-reactivity in polyclonal IgG1 responses against SARS-CoV-2 variants of concern

Author

van Rijswijck, Danique M H, Bondt, Albert, Hoek, Max, van der Straten, Karlijn, Caniels, Tom G, Poniman, Meliawati, Eggink, Dirk, Reusken, Chantal, de Bree, Godelieve J, Sanders, Rogier W, van Gils, Marit J, Heck, Albert J R, van Rijswijck, Danique M H, Bondt, Albert, Hoek, Max, van der Straten, Karlijn, Caniels, Tom G, Poniman, Meliawati, Eggink, Dirk, Reusken, Chantal, de Bree, Godelieve J, Sanders, Rogier W, van Gils, Marit J, and Heck, Albert J R

Abstract

Existing assays to measure antibody cross-reactivity against different SARS-CoV-2 spike (S) protein variants lack the discriminatory power to provide insights at the level of individual clones. Using a mass spectrometry-based approach we are able to monitor individual donors' IgG1 clonal responses following a SARS-CoV-2 infection. We monitor the plasma clonal IgG1 profiles of 8 donors who had experienced an infection by either the wild type Wuhan Hu-1 virus or one of 3 VOCs (Alpha, Beta and Gamma). In these donors we chart the full plasma IgG1 repertoires as well as the IgG1 repertoires targeting the SARS-CoV-2 spike protein trimer VOC antigens. The plasma of each donor contains numerous anti-spike IgG1 antibodies, accounting for <0.1% up to almost 10% of all IgG1s. Some of these antibodies are VOC-specific whereas others do recognize multiple or even all VOCs. We show that in these polyclonal responses, each clone exhibits a distinct cross-reactivity and also distinct virus neutralization capacity. These observations support the need for a more personalized look at the antibody clonal responses to infectious diseases.

Published
2022

21. Co-display of diverse spike proteins on nanoparticles broadens sarbecovirus neutralizing antibody responses

Author

Afd Biomol.Mass Spect. and Proteomics, Sub Biomol.Mass Spectrometry & Proteom., Biomolecular Mass Spectrometry and Proteomics, Brinkkemper, Mitch, Veth, Tim S, Brouwer, Philip J M, Turner, Hannah, Poniman, Meliawati, Burger, Judith A, Bouhuijs, Joey H, Olijhoek, Wouter, Bontjer, Ilja, Snitselaar, Jonne L, Caniels, Tom G, van der Linden, Cynthia A, Ravichandran, Rashmi, Villaudy, Julien, van der Velden, Yme U, Sliepen, Kwinten, van Gils, Marit J, Ward, Andrew B, King, Neil P, Heck, Albert J R, Sanders, Rogier W, Afd Biomol.Mass Spect. and Proteomics, Sub Biomol.Mass Spectrometry & Proteom., Biomolecular Mass Spectrometry and Proteomics, Brinkkemper, Mitch, Veth, Tim S, Brouwer, Philip J M, Turner, Hannah, Poniman, Meliawati, Burger, Judith A, Bouhuijs, Joey H, Olijhoek, Wouter, Bontjer, Ilja, Snitselaar, Jonne L, Caniels, Tom G, van der Linden, Cynthia A, Ravichandran, Rashmi, Villaudy, Julien, van der Velden, Yme U, Sliepen, Kwinten, van Gils, Marit J, Ward, Andrew B, King, Neil P, Heck, Albert J R, and Sanders, Rogier W

Published
2022

22. A single-shot adenoviral vaccine provides hemagglutinin stalk-mediated protection against heterosubtypic influenza challenge in mice

Author

Bliss, Carly M., primary, Freyn, Alec W., additional, Caniels, Tom G., additional, Leyva-Grado, Victor H., additional, Nachbagauer, Raffael, additional, Sun, Weina, additional, Tan, Gene S., additional, Gillespie, Virginia L., additional, McMahon, Meagan, additional, Krammer, Florian, additional, Hill, Adrian V.S., additional, Palese, Peter, additional, and Coughlan, Lynda, additional

Published
2022
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23. IgG1 responses following SARS-CoV-2 infection are polyclonal and highly personalized, whereby each donor and each clone displays a distinct pattern of cross-reactivity against SARS-CoV-2 variants

Author

van Rijswijck, Danique M.H., primary, Bondt, Albert, additional, Hoek, Max, additional, van der Straten, Karlijn, additional, Caniels, Tom G, additional, Poniman, Meliawati, additional, Eggink, Dirk, additional, Reusken, Chantal B.E.M., additional, de Bree, Godelieve J, additional, Sanders, Rogier W., additional, van Gils, Marit, additional, and Heck, Albert J.R., additional

Published
2022
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24. Mapping the antigenic diversification of SARS-CoV-2

Author

van der Straten, Karlijn, primary, Guerra, Denise, additional, van Gils, Marit J., additional, Bontjer, Ilja, additional, Caniels, Tom G., additional, van Willigen, Hugo D.G., additional, Wynberg, Elke, additional, Poniman, Meliawati, additional, Burger, Judith A., additional, Bouhuijs, Joey H., additional, van Rijswijk, Jacqueline, additional, Olijhoek, Wouter, additional, Liesdek, Marinus H., additional, Lavell, A. H. Ayesha, additional, Appelman, Brent, additional, Sikkens, Jonne J., additional, Bomers, Marije K., additional, Han, Alvin X., additional, Nichols, Brooke E., additional, Prins, Maria, additional, Vennema, Harry, additional, Reusken, Chantal, additional, de Jong, Menno D., additional, de Bree, Godelieve J., additional, Russell, Colin A., additional, Eggink, Dirk, additional, and Sanders, Rogier W., additional

Published
2022
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25. A single mRNA vaccine dose in COVID-19 patients boosts neutralizing antibodies against SARS-CoV-2 and variants of concern

Author

van Gils, Marit J., primary, van Willigen, Hugo D.G., additional, Wynberg, Elke, additional, Han, Alvin X., additional, van der Straten, Karlijn, additional, Burger, Judith A., additional, Poniman, Meliawati, additional, Oomen, Melissa, additional, Tejjani, Khadija, additional, Bouhuijs, Joey H., additional, Verveen, Anouk, additional, Lebbink, Romy, additional, Dijkstra, Maartje, additional, Appelman, Brent, additional, Lavell, A.H. Ayesha, additional, Caniels, Tom G., additional, Bontjer, Ilja, additional, van Vught, Lonneke A., additional, Vlaar, Alexander P.J., additional, Sikkens, Jonne J., additional, Bomers, Marije K., additional, Russell, Colin A., additional, Kootstra, Neeltje A., additional, Sanders, Rogier W., additional, Prins, Maria, additional, de Bree, Godelieve J., additional, de Jong, Menno D., additional, Agard, Ivette, additional, Ayal, Jane, additional, Boyd, Anders, additional, Cavdar, Floor, additional, Craanen, Marianne, additional, Davidovich, Udi, additional, Deuring, Annemarieke, additional, van Dijk, Annelies, additional, Ersan, Ertan, additional, del Grande, Laura, additional, Hartman, Joost, additional, Koedoot, Nelleke, additional, Leenstra, Tjalling, additional, Loomans, Dominique, additional, Makowska, Agata, additional, du Maine, Tom, additional, de Man, Ilja, additional, Matser, Amy, additional, van der Meij, Lizenka, additional, van Polanen, Marleen, additional, Oud, Maria, additional, Reid, Clark, additional, Storey, Leeann, additional, de Wit, Marije, additional, van Wijk, Marc, additional, van Assem, Joyce, additional, van den Aardweg, Joost, additional, van Beek, Marijne, additional, Blankert, Thyra, additional, Boeser-Nunnink, Brigitte, additional, Moll van Charante, Eric, additional, van Dort, Karel, additional, Figaroa, Orlane, additional, Frenkel, Leah, additional, Girigorie, Arginell, additional, van Haga, Jelle, additional, Harskamp-Holwerda, Agnes, additional, Hazenberg, Mette, additional, Hidad, Soemeja, additional, de Jong, Nina, additional, Jonges, Marcel, additional, Jurriaans, Suzanne, additional, Knoop, Hans, additional, Kuijt, Lara, additional, Lok, Anja, additional, Ruiz, Marga Mangas, additional, Maurer, Irma, additional, Nieuwkerk, Pythia, additional, van Nuenen, Ad, additional, van der Veen, Annelou, additional, Verkaik, Bas, additional, and Visser, Gerben-Rienk, additional

Published
2022
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26. HIV-1 Germline-Targeting Vaccine Regimen Selects for Rare Immunoglobulin Insertions and Deletions Typical of VRC01-Class Antibodies

Author

Caniels, Tom G., primary, Medina-Ramírez, Max, additional, Zhang, Jinsong, additional, Sarkar, Anita, additional, Kumar, Sonu, additional, LaBranche, Alex, additional, Derking, Ronald, additional, Allen, Joel D., additional, Snitselaar, Jonne L., additional, Capella-Pujol, Joan, additional, del Moral Sánchez, Iván, additional, Yasmeen, Anila, additional, Diaz, Marilyn, additional, Aldon, Yoann, additional, Bijl, Tom PL, additional, Venkatayogi, Sravani, additional, Martin Beem, Joshua S., additional, Newman, Amanda, additional, Jiang, Chuancang, additional, Lee, Wen-Hsin, additional, Pater, Maarten, additional, Burger, Judith A., additional, van Breemen, Mariëlle J., additional, LaBranche, Celia C., additional, Saunders, Kevin O., additional, Montefiori, David C., additional, Ozorowski, Gabriel, additional, Ward, Andrew B., additional, Crispin, Max, additional, Moore, John P., additional, Klasse, Per Johan, additional, Haynes, Barton F., additional, Wilson, Ian, additional, Wiehe, Kevin, additional, Verkoczy, Laurent, additional, and Sanders, Rogier, additional

Published
2022
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27. A public antibody class recognizes a novel S2 epitope exposed on open conformations of SARS-CoV-2 spike

Author

Claireaux, Mathieu, primary, Caniels, Tom G, additional, de Gast, Marlon, additional, Han, Julianna, additional, Guerra, Denise, additional, Kerster, Gius, additional, van Schaik, Barbera DC, additional, Jongejan, Aldo, additional, Schriek, Angela I., additional, Grobben, Marloes, additional, Brouwer, Philip JM, additional, van der Straten, Karlijn, additional, Aldon, Yoann, additional, Capella-Pujol, Joan, additional, Snitselaar, Jonne L, additional, Olijhoek, Wouter, additional, Aartse, Aafke, additional, Brinkkemper, Mitch, additional, Bontjer, Ilja, additional, Burger, Judith A, additional, Poniman, Meliawati, additional, Bijl, Tom PL, additional, Torres, Jonathan L, additional, Copps, Jeffrey, additional, Martin, Isabel Cuella, additional, de Taeye, Steven W, additional, de Bree, Godelieve J, additional, Ward, Andrew B, additional, Sliepen, Kwinten, additional, van Kampen, Antoine HC, additional, Moerland, Perry D, additional, Sanders, Rogier W, additional, and van Gils, Marit J, additional

Published
2021
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28. Probing Affinity, Avidity, Anti-Cooperativity, and Competition in Antibody and Receptor Binding to the SARS-CoV-2 Spike by Single Particle Mass Analyses

Author

Yin, Victor, Lai, Szu-Hsueh, Caniels, Tom G, Brouwer, Philip J M, Brinkkemper, Mitch, Aldon, Yoann, Liu, Hejun, Yuan, Meng, Wilson, Ian A, Sanders, Rogier W, van Gils, Marit J, Heck, Albert J R, Sub Biomol.Mass Spectrometry & Proteom., Afd Biomol.Mass Spect. and Proteomics, Biomolecular Mass Spectrometry and Proteomics, Sub Biomol.Mass Spectrometry & Proteom., Afd Biomol.Mass Spect. and Proteomics, Biomolecular Mass Spectrometry and Proteomics, Graduate School, Medical Microbiology and Infection Prevention, and AII - Infectious diseases

Subjects
Steric effects, Chemistry(all), biology, Chemistry, General Chemical Engineering, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Cooperativity, General Chemistry, Mass spectrometry, Antigen, Ectodomain, IgG binding, Chemical Engineering(all), biology.protein, Biophysics, Avidity, Antibody, QD1-999, Research Article
Abstract

Determining how antibodies interact with the spike (S) protein of the SARS-CoV-2 virus is critical for combating COVID-19. Structural studies typically employ simplified, truncated constructs that may not fully recapitulate the behavior of the original complexes. Here, we combine two single particle mass analysis techniques (mass photometry and charge-detection mass spectrometry) to enable the measurement of full IgG binding to the trimeric SARS-CoV-2 S ectodomain. Our experiments reveal that antibodies targeting the S-trimer typically prefer stoichiometries lower than the symmetry-predicted 3:1 binding. We determine that this behavior arises from the interplay of steric clashes and avidity effects that are not reflected in common antibody constructs (i.e., Fabs). Surprisingly, these substoichiometric complexes are fully effective at blocking ACE2 binding despite containing free receptor binding sites. Our results highlight the importance of studying antibody/antigen interactions using complete, multimeric constructs and showcase the utility of single particle mass analyses in unraveling these complex interactions., Single particle mass analysis methods unravel the complex multimeric interactions that occur between neutralizing IgG antibodies, the ACE2 receptor, and the trimeric, glycosylated SARS-CoV-2 spike.

Published
2021

29. Probing Affinity, Avidity, Anticooperativity, and Competition in Antibody and Receptor Binding to the SARS-CoV-2 Spike by Single Particle Mass Analyses

Author

Yin, Victor, primary, Lai, Szu-Hsueh, additional, Caniels, Tom G., additional, Brouwer, Philip J. M., additional, Brinkkemper, Mitch, additional, Aldon, Yoann, additional, Liu, Hejun, additional, Yuan, Meng, additional, Wilson, Ian A., additional, Sanders, Rogier W., additional, van Gils, Marit J., additional, and Heck, Albert J. R., additional

Published
2021
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31. Probing Affinity, Avidity, Anti-Cooperativity, and Competition in Antibody and Receptor Binding to the SARS-CoV-2 Spike by Single Particle Mass Analyses

Author

Yin, Victor, primary, Lai, Szu-Hsueh, additional, Caniels, Tom G., additional, Brouwer, Philip J.M., additional, Brinkkemper, Mitch, additional, Aldon, Yoann, additional, Liu, Hejun, additional, Yuan, Meng, additional, Wilson, Ian A., additional, Sanders, Rogier W., additional, van Gils, Marit J., additional, and Heck, Albert J.R., additional

Published
2021
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32. High titers and low fucosylation of early human anti–SARS-CoV-2 IgG promote inflammation by alveolar macrophages

Author

Hoepel, Willianne, primary, Chen, Hung-Jen, additional, Geyer, Chiara E., additional, Allahverdiyeva, Sona, additional, Manz, Xue D., additional, de Taeye, Steven W., additional, Aman, Jurjan, additional, Mes, Lynn, additional, Steenhuis, Maurice, additional, Griffith, Guillermo R., additional, Bonta, Peter I., additional, Brouwer, Philip J.M., additional, Caniels, Tom G., additional, van der Straten, Karlijn, additional, Golebski, Korneliusz, additional, Jonkers, René E., additional, Larsen, Mads D., additional, Linty, Federica, additional, Nouta, Jan, additional, van Roomen, Cindy P.A.A., additional, van Baarle, Frank E.H.P., additional, van Drunen, Cornelis M., additional, Wolbink, Gertjan, additional, Vlaar, Alexander P.J., additional, de Bree, Godelieve J., additional, Sanders, Rogier W., additional, Willemsen, Lisa, additional, Neele, Annette E., additional, van de Beek, Diederik, additional, Rispens, Theo, additional, Wuhrer, Manfred, additional, Bogaard, Harm Jan, additional, van Gils, Marit J., additional, Vidarsson, Gestur, additional, de Winther, Menno, additional, and den Dunnen, Jeroen, additional

Published
2021
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33. Probing Affinity, Avidity, Anticooperativity, and Competition in Antibody and Receptor Binding to the SARS-CoV-2 Spike by Single Particle Mass Analyses

Author

Yin, Victor, Lai, Szu-Hsueh, Caniels, Tom G, Brouwer, Philip J M, Brinkkemper, Mitch, Aldon, Yoann, Liu, Hejun, Yuan, Meng, Wilson, Ian A, Sanders, Rogier W, van Gils, Marit J, Heck, Albert J R, Yin, Victor, Lai, Szu-Hsueh, Caniels, Tom G, Brouwer, Philip J M, Brinkkemper, Mitch, Aldon, Yoann, Liu, Hejun, Yuan, Meng, Wilson, Ian A, Sanders, Rogier W, van Gils, Marit J, and Heck, Albert J R

Abstract

Determining how antibodies interact with the spike (S) protein of the SARS-CoV-2 virus is critical for combating COVID-19. Structural studies typically employ simplified, truncated constructs that may not fully recapitulate the behavior of the original complexes. Here, we combine two single particle mass analysis techniques (mass photometry and charge-detection mass spectrometry) to enable the measurement of full IgG binding to the trimeric SARS-CoV-2 S ectodomain. Our experiments reveal that antibodies targeting the S-trimer typically prefer stoichiometries lower than the symmetry-predicted 3:1 binding. We determine that this behavior arises from the interplay of steric clashes and avidity effects that are not reflected in common antibody constructs (i.e., Fabs). Surprisingly, these substoichiometric complexes are fully effective at blocking ACE2 binding despite containing free receptor binding sites. Our results highlight the importance of studying antibody/antigen interactions using complete, multimeric constructs and showcase the utility of single particle mass analyses in unraveling these complex interactions.

Published
2021

34. Probing Affinity, Avidity, Anticooperativity, and Competition in Antibody and Receptor Binding to the SARS-CoV-2 Spike by Single Particle Mass Analyses

Author

Sub Biomol.Mass Spectrometry & Proteom., Afd Biomol.Mass Spect. and Proteomics, Biomolecular Mass Spectrometry and Proteomics, Yin, Victor, Lai, Szu-Hsueh, Caniels, Tom G, Brouwer, Philip J M, Brinkkemper, Mitch, Aldon, Yoann, Liu, Hejun, Yuan, Meng, Wilson, Ian A, Sanders, Rogier W, van Gils, Marit J, Heck, Albert J R, Sub Biomol.Mass Spectrometry & Proteom., Afd Biomol.Mass Spect. and Proteomics, Biomolecular Mass Spectrometry and Proteomics, Yin, Victor, Lai, Szu-Hsueh, Caniels, Tom G, Brouwer, Philip J M, Brinkkemper, Mitch, Aldon, Yoann, Liu, Hejun, Yuan, Meng, Wilson, Ian A, Sanders, Rogier W, van Gils, Marit J, and Heck, Albert J R

Published
2021

35. Two-component spike nanoparticle vaccine protects macaques from SARS-CoV-2 infection

Author

Brouwer, Philip J.M., Brinkkemper, Mitch, Maisonnasse, Pauline, Dereuddre-Bosquet, Nathalie, Grobben, Marloes, Claireaux, Mathieu, de Gast, Marlon, Marlin, Romain, Chesnais, Virginie, Diry, Ségolène, Allen, Joel D., Watanabe, Yasunori, Giezen, Julia M., Kerster, Gius, Turner, Hannah L., van der Straten, Karlijn, van der Linden, Cynthia A., Aldon, Yoann, Naninck, Thibaut, Bontjer, Ilja, Burger, Judith A., Poniman, Meliawati, Mykytyn, Anna Z., Okba, Nisreen M.A., Schermer, Edith E., van Breemen, Marielle J., Ravichandran, Rashmi, Caniels, Tom G., van Schooten, Jelle, Kahlaoui, Nidhal, Contreras, Vanessa, Lemaître, Julien, Chapon, Catherine, Fang, Raphaël Ho Tsong, Villaudy, Julien, Sliepen, Kwinten, van der Velden, Yme U., Haagmans, Bart L., de Bree, Godelieve J., Ginoux, Eric, Ward, Andrew B., Crispin, Max, King, Neil P., van der Werf, Sylvie, van Gils, Marit J., Le Grand, Roger, Sanders, Rogier W., Brouwer, Philip J.M., Brinkkemper, Mitch, Maisonnasse, Pauline, Dereuddre-Bosquet, Nathalie, Grobben, Marloes, Claireaux, Mathieu, de Gast, Marlon, Marlin, Romain, Chesnais, Virginie, Diry, Ségolène, Allen, Joel D., Watanabe, Yasunori, Giezen, Julia M., Kerster, Gius, Turner, Hannah L., van der Straten, Karlijn, van der Linden, Cynthia A., Aldon, Yoann, Naninck, Thibaut, Bontjer, Ilja, Burger, Judith A., Poniman, Meliawati, Mykytyn, Anna Z., Okba, Nisreen M.A., Schermer, Edith E., van Breemen, Marielle J., Ravichandran, Rashmi, Caniels, Tom G., van Schooten, Jelle, Kahlaoui, Nidhal, Contreras, Vanessa, Lemaître, Julien, Chapon, Catherine, Fang, Raphaël Ho Tsong, Villaudy, Julien, Sliepen, Kwinten, van der Velden, Yme U., Haagmans, Bart L., de Bree, Godelieve J., Ginoux, Eric, Ward, Andrew B., Crispin, Max, King, Neil P., van der Werf, Sylvie, van Gils, Marit J., Le Grand, Roger, and Sanders, Rogier W.

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is continuing to disrupt personal lives, global healthcare systems, and economies. Hence, there is an urgent need for a vaccine that prevents viral infection, transmission, and disease. Here, we present a two-component protein-based nanoparticle vaccine that displays multiple copies of the SARS-CoV-2 spike protein. Immunization studies show that this vaccine induces potent neutralizing antibody responses in mice, rabbits, and cynomolgus macaques. The vaccine-induced immunity protects macaques against a high-dose challenge, resulting in strongly reduced viral infection and replication in the upper and lower airways. These nanoparticles are a promising vaccine candidate to curtail the SARS-CoV-2 pandemic. Brouwer et al. present preclinical evidence in support of a COVID-19 vaccine candidate, designed as a self-assembling two-component protein nanoparticle displaying multiple copies of the SARS-CoV-2 spike protein, which induces strong neutralizing antibody responses and protects from high-dose SARS-CoV-2 challenge.

Published
2021

36. SARS-CoV-2 variants of concern partially escape humoral but not T-cell responses in COVID-19 convalescent donors and vaccinees

Author

Geers, Daryl, Shamier, Marc C., Bogers, Susanne, den Hartog, Gerco, Gommers, Lennert, Nieuwkoop, Nella N., Schmitz, Katharina S., Rijsbergen, Laurine C., van Osch, Jolieke A.T., Dijkhuizen, Emma, Smits, Gaby, Comvalius, Anouskha, van Mourik, Djenolan, Caniels, Tom G., van Gils, Marit J., Sanders, Rogier W., Oude Munnink, Bas B., Molenkamp, Richard, de Jager, Herbert J., Haagmans, Bart L., de Swart, Rik L., Koopmans, Marion P.G., van Binnendijk, Robert S., de Vries, Rory D., GeurtsvanKessel, Corine H., Geers, Daryl, Shamier, Marc C., Bogers, Susanne, den Hartog, Gerco, Gommers, Lennert, Nieuwkoop, Nella N., Schmitz, Katharina S., Rijsbergen, Laurine C., van Osch, Jolieke A.T., Dijkhuizen, Emma, Smits, Gaby, Comvalius, Anouskha, van Mourik, Djenolan, Caniels, Tom G., van Gils, Marit J., Sanders, Rogier W., Oude Munnink, Bas B., Molenkamp, Richard, de Jager, Herbert J., Haagmans, Bart L., de Swart, Rik L., Koopmans, Marion P.G., van Binnendijk, Robert S., de Vries, Rory D., and GeurtsvanKessel, Corine H.

Abstract

The emergence of SARS-CoV-2 variants harboring mutations in the spike (S) protein has raised concern about potential immune escape. Here, we studied humoral and cellular immune responses to wild type SARS-CoV-2 and the B.1.1.7 and B.1.351 variants of concern in a cohort of 121 BNT162b2 mRNA-vaccinated health care workers (HCW). Twenty-three HCW recovered from mild COVID-19 disease and exhibited a recall response with high levels of SARS-CoV-2-specific functional antibodies and virus-specific T cells after a single vaccination. Specific immune responses were also detected in seronegative HCW after one vaccination, but a second dose was required to reach high levels of functional antibodies and cellular immune responses in all individuals. Vaccination-induced antibodies cross-neutralized the variants B.1.1.7 and B.1.351, but the neutralizing capacity and Fc-mediated functionality against B.1.351 was consistently 2-to 4-fold lower than to the homologous virus. In addition, peripheral blood mononuclear cells were stimulated with peptide pools spanning the mutated S regions of B.1.1.7 and B.1.351 to detect cross-reactivity of SARS-CoV-2-specific T cells with variants. Importantly, we observed no differences in CD4+ T-cell activation in response to variant antigens, indicating that the B.1.1.7 and B.1.351 S proteins do not escape T-cell-mediated immunity elicited by the wild type S protein. In conclusion, this study shows that some variants can partially escape humoral immunity induced by SARS-CoV-2 infection or BNT162b2 vaccination, but S-specific CD4+ T-cell activation is not affected by the mutations in the B.1.1.7 and B.1.351 variants.

Published
2021

37. SARS-CoV-2 variants of concern partially escape humoral but not T cell responses in COVID-19 convalescent donors and vaccine recipients

Author

Geers, Daryl, primary, Shamier, Marc C., additional, Bogers, Susanne, additional, den Hartog, Gerco, additional, Gommers, Lennert, additional, Nieuwkoop, Nella N., additional, Schmitz, Katharina S., additional, Rijsbergen, Laurine C., additional, van Osch, Jolieke A. T., additional, Dijkhuizen, Emma, additional, Smits, Gaby, additional, Comvalius, Anouskha, additional, van Mourik, Djenolan, additional, Caniels, Tom G., additional, van Gils, Marit J., additional, Sanders, Rogier W., additional, Oude Munnink, Bas B., additional, Molenkamp, Richard, additional, de Jager, Herbert J., additional, Haagmans, Bart L., additional, de Swart, Rik L., additional, Koopmans, Marion P. G., additional, van Binnendijk, Robert S., additional, de Vries, Rory D., additional, and GeurtsvanKessel, Corine H., additional

Published
2021
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38. Two-component spike nanoparticle vaccine protects macaques from SARS-CoV-2 infection

Author

Brouwer, Philip J.M., primary, Brinkkemper, Mitch, additional, Maisonnasse, Pauline, additional, Dereuddre-Bosquet, Nathalie, additional, Grobben, Marloes, additional, Claireaux, Mathieu, additional, de Gast, Marlon, additional, Marlin, Romain, additional, Chesnais, Virginie, additional, Diry, Ségolène, additional, Allen, Joel D., additional, Watanabe, Yasunori, additional, Giezen, Julia M., additional, Kerster, Gius, additional, Turner, Hannah L., additional, van der Straten, Karlijn, additional, van der Linden, Cynthia A., additional, Aldon, Yoann, additional, Naninck, Thibaut, additional, Bontjer, Ilja, additional, Burger, Judith A., additional, Poniman, Meliawati, additional, Mykytyn, Anna Z., additional, Okba, Nisreen M.A., additional, Schermer, Edith E., additional, van Breemen, Marielle J., additional, Ravichandran, Rashmi, additional, Caniels, Tom G., additional, van Schooten, Jelle, additional, Kahlaoui, Nidhal, additional, Contreras, Vanessa, additional, Lemaître, Julien, additional, Chapon, Catherine, additional, Fang, Raphaël Ho Tsong, additional, Villaudy, Julien, additional, Sliepen, Kwinten, additional, van der Velden, Yme U., additional, Haagmans, Bart L., additional, de Bree, Godelieve J., additional, Ginoux, Eric, additional, Ward, Andrew B., additional, Crispin, Max, additional, King, Neil P., additional, van der Werf, Sylvie, additional, van Gils, Marit J., additional, Le Grand, Roger, additional, and Sanders, Rogier W., additional

Published
2021
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39. Cross-Neutralization of a SARS-CoV-2 Antibody to a Functionally Conserved Site Is Mediated by Avidity

Author

Liu, Hejun, primary, Wu, Nicholas C., additional, Yuan, Meng, additional, Bangaru, Sandhya, additional, Torres, Jonathan L., additional, Caniels, Tom G., additional, van Schooten, Jelle, additional, Zhu, Xueyong, additional, Lee, Chang-Chun D., additional, Brouwer, Philip J.M., additional, van Gils, Marit J., additional, Sanders, Rogier W., additional, Ward, Andrew B., additional, and Wilson, Ian A., additional

Published
2020
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40. Two-component spike nanoparticle vaccine protects macaques from SARS-CoV-2 infection

Author

Brouwer, Philip J. M., primary, Brinkkemper, Mitch, additional, Maisonnasse, Pauline, additional, Dereuddre-Bosquet, Nathalie, additional, Grobben, Marloes, additional, Claireaux, Mathieu, additional, de Gast, Marlon, additional, Marlin, Romain, additional, Chesnais, Virginie, additional, Diry, Ségolène, additional, Allen, Joel D., additional, Watanabe, Yasunori, additional, Giezen, Julia M., additional, Kerster, Gius, additional, Turner, Hannah L., additional, van der Straten, Karlijn, additional, van der Linden, Cynthia A., additional, Aldon, Yoann, additional, Naninck, Thibaut, additional, Bontjer, Ilja, additional, Burger, Judith A., additional, Poniman, Meliawati, additional, Mykytyn, Anna Z., additional, Okba, Nisreen M. A., additional, Schermer, Edith E., additional, van Breemen, Marielle J., additional, Ravichandran, Rashmi, additional, Caniels, Tom G., additional, van Schooten, Jelle, additional, Kahlaoui, Nidhal, additional, Contreras, Vanessa, additional, Lemaître, Julien, additional, Chapon, Catherine, additional, Ho Tsong Fang, Raphaël, additional, Villaudy, Julien, additional, Sliepen, Kwinten, additional, van der Velden, Yme U., additional, Haagmans, Bart L., additional, de Bree, Godelieve J., additional, Ginoux, Eric, additional, Ward, Andrew B., additional, Crispin, Max, additional, King, Neil P., additional, van der Werf, Sylvie, additional, van Gils, Marit J., additional, Grand, Roger Le, additional, and Sanders, Rogier W., additional

Published
2020
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41. An Alternative Binding Mode of IGHV3-53 Antibodies to the SARS-CoV-2 Receptor Binding Domain

Author

Wu, Nicholas C., primary, Yuan, Meng, additional, Liu, Hejun, additional, Lee, Chang-Chun D., additional, Zhu, Xueyong, additional, Bangaru, Sandhya, additional, Torres, Jonathan L., additional, Caniels, Tom G., additional, Brouwer, Philip J.M., additional, van Gils, Marit J., additional, Sanders, Rogier W., additional, Ward, Andrew B., additional, and Wilson, Ian A., additional

Published
2020
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42. Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability

Author

Brouwer, Philip J. M., primary, Caniels, Tom G., additional, van der Straten, Karlijn, additional, Snitselaar, Jonne L., additional, Aldon, Yoann, additional, Bangaru, Sandhya, additional, Torres, Jonathan L., additional, Okba, Nisreen M. A., additional, Claireaux, Mathieu, additional, Kerster, Gius, additional, Bentlage, Arthur E. H., additional, van Haaren, Marlies M., additional, Guerra, Denise, additional, Burger, Judith A., additional, Schermer, Edith E., additional, Verheul, Kirsten D., additional, van der Velde, Niels, additional, van der Kooi, Alex, additional, van Schooten, Jelle, additional, van Breemen, Mariëlle J., additional, Bijl, Tom P. L., additional, Sliepen, Kwinten, additional, Aartse, Aafke, additional, Derking, Ronald, additional, Bontjer, Ilja, additional, Kootstra, Neeltje A., additional, Wiersinga, W. Joost, additional, Vidarsson, Gestur, additional, Haagmans, Bart L., additional, Ward, Andrew B., additional, de Bree, Godelieve J., additional, Sanders, Rogier W., additional, and van Gils, Marit J., additional

Published
2020
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43. Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability

Author

Brouwer, Philip J.M., primary, Caniels, Tom G., additional, van der Straten, Karlijn, additional, Snitselaar, Jonne L., additional, Aldon, Yoann, additional, Bangaru, Sandhya, additional, Torres, Jonathan L., additional, Okba, Nisreen M.A., additional, Claireaux, Mathieu, additional, Kerster, Gius, additional, Bentlage, Arthur E.H., additional, van Haaren, Marlies M., additional, Guerra, Denise, additional, Burger, Judith A., additional, Schermer, Edith E., additional, Verheul, Kirsten D., additional, van der Velde, Niels, additional, van der Kooi, Alex, additional, van Schooten, Jelle, additional, van Breemen, Mariëlle J., additional, Bijl, Tom P. L., additional, Sliepen, Kwinten, additional, Aartse, Aafke, additional, Derking, Ronald, additional, Bontjer, Ilja, additional, Kootstra, Neeltje A., additional, Wiersinga, W. Joost, additional, Vidarsson, Gestur, additional, Haagmans, Bart L., additional, Ward, Andrew B., additional, de Bree, Godelieve J., additional, Sanders, Rogier W., additional, and van Gils, Marit J., additional

Published
2020
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44. Emerging SARS-CoV-2 variants of concern evade humoral immune responses from infection and vaccination.

Author

Caniels, Tom G., Bontjer, Ilja, van der Straten, Karlijn, Poniman, Meliawati, Burger, Judith A., Appelman, Brent, Lavell, H. A. Ayesha, Oomen, Melissa, Godeke, Gert-Jan, Valle, Coralie, Mögling, Ramona, van Willigen, Hugo D. G., Wynberg, Elke, Schinkel, Michiel, van Vught, Lonneke A., Guerra, Denise, Snitselaar, Jonne L., Chaturbhuj, Devidas N., Martin, Isabel Cuella, and Moore, John P.

Subjects
*SARS-CoV-2, *COVID-19, *HUMORAL immunity, *MEDICAL personnel, *REVERSE transcriptase polymerase chain reaction
Published
2021
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45. Plant‐produced SARS‐CoV‐2 antibody engineered towards enhanced potency and in vivo efficacy.

Author

Taeye, Steven W., Faye, Loïc, Morel, Bertrand, Schriek, Angela I., Umotoy, Jeffrey C., Yuan, Meng, Kuzmina, Natalia A., Turner, Hannah L., Zhu, Xueyong, Grünwald‐Gruber, Clemens, Poniman, Meliawati, Burger, Judith A., Caniels, Tom G., Fitchette, Anne‐Catherine, Desgagnés, Réjean, Stordeur, Virginie, Mirande, Lucie, Beauverger, Guillaume, Bree, Godelieve, and Ozorowski, Gabriel

Abstract

Summary Prevention of severe COVID‐19 disease by SARS‐CoV‐2 in high‐risk patients, such as immuno‐compromised individuals, can be achieved by administration of antibody prophylaxis, but producing antibodies can be costly. Plant expression platforms allow substantial lower production costs compared to traditional bio‐manufacturing platforms depending on mammalian cells in bioreactors. In this study, we describe the expression, production and purification of the originally human COVA2‐15 antibody in plants. Our plant‐produced mAbs demonstrated comparable neutralizing activity with COVA2‐15 produced in mammalian cells. Furthermore, they exhibited similar capacity to prevent SARS‐CoV‐2 infection in a hamster model. To further enhance these biosimilars, we performed three glyco‐ and protein engineering techniques. First, to increase antibody half‐life, we introduced YTE‐mutation in the Fc tail; second, optimization of N‐linked glycosylation by the addition of a C‐terminal ER‐retention motif (HDEL), and finally; production of mAb in plant production lines lacking β‐1,2‐xylosyltransferase and α‐1,3‐fucosyltransferase activities (FX‐KO). These engineered biosimilars exhibited optimized glycosylation, enhanced phagocytosis and NK cell activation capacity compared to conventional plant‐produced S15 and M15 biosimilars, in some cases outperforming mammalian cell produced COVA2‐15. These engineered antibodies hold great potential for enhancing in vivo efficacy of mAb treatment against COVID‐19 and provide a platform for the development of antibodies against other emerging viruses in a cost‐effective manner. [ABSTRACT FROM AUTHOR]

Published
2024
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46. A single mRNA vaccine dose in COVID-19 patients boosts neutralizing antibodies against SARS-CoV-2 and variants of concern

Author

van Gils, Marit J., van Willigen, Hugo D.G., Wynberg, Elke, Han, Alvin X., van der Straten, Karlijn, Burger, Judith A., Poniman, Meliawati, Oomen, Melissa, Tejjani, Khadija, Bouhuijs, Joey H., Verveen, Anouk, Lebbink, Romy, Dijkstra, Maartje, Appelman, Brent, Lavell, A.H. Ayesha, Caniels, Tom G., Bontjer, Ilja, van Vught, Lonneke A., Vlaar, Alexander P.J., Sikkens, Jonne J., Bomers, Marije K., Russell, Colin A., Kootstra, Neeltje A., Sanders, Rogier W., Prins, Maria, de Bree, Godelieve J., and de Jong, Menno D.

Abstract

The urgent need for, but limited availability of, SARS-CoV-2 vaccines worldwide has led to widespread consideration of dose-sparing strategies. Here, we evaluate the SARS-CoV-2-specific antibody responses following BNT162b2 vaccination in 150 previously SARS-CoV-2-infected individuals from a population-based cohort. One week after first vaccine dose, spike protein antibody levels are 27-fold higher and neutralizing antibody titers 12-fold higher, exceeding titers of fully vaccinated SARS-CoV-2-naive controls, with minimal additional boosting after the second dose. Neutralizing antibody titers against four variants of concern increase after vaccination; however, overall neutralization breadth does not improve. Pre-vaccination neutralizing antibody titers and time since infection have the largest positive effect on titers following vaccination. COVID-19 severity and the presence of comorbidities have no discernible impact on vaccine response. In conclusion, a single dose of BNT162b2 vaccine up to 15 months after SARS-CoV-2 infection offers higher neutralizing antibody titers than 2 vaccine doses in SARS-CoV-2-naive individuals.

Published
2021
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47. Plant-produced SARS-CoV-2 antibody engineered towards enhanced potency and in vivo efficacy.

Author

de Taeye SW, Faye L, Morel B, Schriek AI, Umotoy JC, Yuan M, Kuzmina NA, Turner HL, Zhu X, Grünwald-Gruber C, Poniman M, Burger JA, Caniels TG, Fitchette AC, Desgagnés R, Stordeur V, Mirande L, Beauverger G, de Bree G, Ozorowski G, Ward AB, Wilson IA, Bukreyev A, Sanders RW, Vezina LP, Beaumont T, van Gils MJ, and Gomord V

Abstract

Prevention of severe COVID-19 disease by SARS-CoV-2 in high-risk patients, such as immuno-compromised individuals, can be achieved by administration of antibody prophylaxis, but producing antibodies can be costly. Plant expression platforms allow substantial lower production costs compared to traditional bio-manufacturing platforms depending on mammalian cells in bioreactors. In this study, we describe the expression, production and purification of the originally human COVA2-15 antibody in plants. Our plant-produced mAbs demonstrated comparable neutralizing activity with COVA2-15 produced in mammalian cells. Furthermore, they exhibited similar capacity to prevent SARS-CoV-2 infection in a hamster model. To further enhance these biosimilars, we performed three glyco- and protein engineering techniques. First, to increase antibody half-life, we introduced YTE-mutation in the Fc tail; second, optimization of N-linked glycosylation by the addition of a C-terminal ER-retention motif (HDEL), and finally; production of mAb in plant production lines lacking β-1,2-xylosyltransferase and α-1,3-fucosyltransferase activities (FX-KO). These engineered biosimilars exhibited optimized glycosylation, enhanced phagocytosis and NK cell activation capacity compared to conventional plant-produced S15 and M15 biosimilars, in some cases outperforming mammalian cell produced COVA2-15. These engineered antibodies hold great potential for enhancing in vivo efficacy of mAb treatment against COVID-19 and provide a platform for the development of antibodies against other emerging viruses in a cost-effective manner., (© 2024 The Author(s). Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.)

Published
2024
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48. Identification of new drugs to counteract anti-spike IgG-induced hyperinflammation in severe COVID-19.

Author

Geyer CE, Chen HJ, Bye AP, Manz XD, Guerra D, Caniels TG, Bijl TP, Griffith GR, Hoepel W, de Taeye SW, Veth J, Vlaar AP, Vidarsson G, Bogaard HJ, Aman J, Gibbins JM, van Gils MJ, de Winther MP, and den Dunnen J

Subjects
Humans, SARS-CoV-2, Antibodies, Viral, Inflammation drug therapy, Immunoglobulin G pharmacology, COVID-19
Abstract

Previously, we and others have shown that SARS-CoV-2 spike-specific IgG antibodies play a major role in disease severity in COVID-19 by triggering macrophage hyperactivation, disrupting endothelial barrier integrity, and inducing thrombus formation. This hyperinflammation is dependent on high levels of anti-spike IgG with aberrant Fc tail glycosylation, leading to Fcγ receptor hyperactivation. For development of immune-regulatory therapeutics, drug specificity is crucial to counteract excessive inflammation whereas simultaneously minimizing the inhibition of antiviral immunity. We here developed an in vitro activation assay to screen for small molecule drugs that specifically counteract antibody-induced pathology. We identified that anti-spike-induced inflammation is specifically blocked by small molecule inhibitors against SYK and PI3K. We identified SYK inhibitor entospletinib as the most promising candidate drug, which also counteracted anti-spike-induced endothelial dysfunction and thrombus formation. Moreover, entospletinib blocked inflammation by different SARS-CoV-2 variants of concern. Combined, these data identify entospletinib as a promising treatment for severe COVID-19., (© 2023 Geyer et al.)

Published
2023
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49. The SARS-CoV-2 spike N-terminal domain engages 9- O -acetylated α2-8-linked sialic acids.

Author

Tomris I, Unione L, Nguyen L, Zaree P, Bouwman KM, Liu L, Li Z, Fok JA, Ríos Carrasco M, van der Woude R, Kimpel ALM, Linthorst MW, Verpalen ECJM, Caniels TG, Sanders RW, Heesters BA, Pieters RJ, Jiménez-Barbero J, Klassen JS, Boons GJ, and de Vries RP

Abstract

SARS-CoV-2 viruses engage ACE2 as a functional receptor with their spike protein. The S1 domain of the spike protein contains a C-terminal receptor-binding domain (RBD) and an N-terminal domain (NTD). The NTD of other coronaviruses includes a glycan-binding cleft. However, for the SARS-CoV-2 NTD protein-glycan binding was only observed weakly for sialic acids with highly sensitive methods. Amino acid changes in the NTD of Variants of Concern (VoC) shows antigenic pressure, which can be an indication of NTD-mediated receptor binding. Trimeric NTD proteins of SARS-CoV-2, Alpha, Beta, Delta, and Omicron did not reveal a receptor binding capability. Unexpectedly, the SARS-CoV-2 Beta subvariant strain (501Y.V2-1) NTD binding to Vero E6 cells was sensitive to sialidase pretreatment. Glycan microarray analyses identified a putative 9- O -acetylated sialic acid as a ligand, which was confirmed by catch-and-release ESI-MS, STD-NMR analyses, and a graphene-based electrochemical sensor. The Beta (501Y.V2-1) variant attained an enhanced glycan binding modality in the NTD with specificity towards 9- O -acetylated structures, suggesting a dual-receptor functionality of the SARS-CoV-2 S1 domain, which was quickly selected against. These results indicate that SARS-CoV-2 can probe additional evolutionary space, allowing binding to glycan receptors on the surface of target cells., Synopsis: Coronaviruses utilize their N-terminal domain (NTD) for initial reversible low-affinity interaction to (sialylated) glycans. This initial low-affinity/high-avidity engagement enables viral surfing on the target membrane, potentially followed by a stronger secondary receptor interaction. Several coronaviruses, such as HKU1 and OC43, possess a hemagglutinin-esterase for viral release after sialic acid interaction, thus allowing viral dissemination. Other coronaviruses, such as MERS-CoV, do not possess a hemagglutinin-esterase, but interact reversibly to sialic acids allowing for viral surfing and dissemination. The early 501Y.V2-1 subvariant of the Beta SARS-CoV-2 Variant of Concern has attained a receptor-binding functionality towards 9- O -acetylated sialic acid using its NTD. This binding functionality was selected against rapidly, most likely due to poor dissemination. Ablation of sialic acid binding in more recent SARS-CoV-2 Variants of Concern suggests a fine balance of sialic acid interaction of SARS-CoV-2 is required for infection and/or transmission.

Published
2022
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50. Broad SARS-CoV-2 Neutralization by Monoclonal and Bispecific Antibodies Derived from a Gamma-infected Individual.

Author

Guerra D, Beaumont T, RadiÄ L, Kerster G, van der Straten K, Yuan M, Torres JL, Lee WH, Liu H, Poniman M, Bontjer I, Burger JA, Claireaux M, Caniels TG, Snitselaar JL, Bijl TPL, Kruijer S, Ozorowski G, Gideonse D, Sliepen K, Ward AB, Eggink D, de Bree GJ, Wilson IA, Sanders RW, and van Gils MJ

Abstract

The worldwide pandemic caused by SARS-CoV-2 has remained a human medical threat due to the continued evolution of multiple variants that acquire resistance to vaccines and prior infection. Therefore, it is imperative to discover monoclonal antibodies (mAbs) that neutralize a broad range of SARS-CoV-2 variants for therapeutic and prophylactic use. A stabilized autologous SARS-CoV-2 spike glycoprotein was used to enrich antigen-specific B cells from an individual with a primary Gamma variant infection. Five mAbs selected from those B cells showed considerable neutralizing potency against multiple variants of concern, with COVA309-35 being the most potent against the autologous virus, as well as against Omicron BA.1 and BA.2. When combining the COVA309 mAbs as cocktails or bispecific antibody formats, the breadth and potency was significantly improved against all tested variants. In addition, the mechanism of cross-neutralization of the COVA309 mAbs was elucidated by structural analysis. Altogether these data indicate that a Gamma-infected individual can develop broadly neutralizing antibodies.

Published
2022
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