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15 results on '"Kuppeveld, Frank J. M Van"'

1. Nanoparticle display of neuraminidase elicits enhanced antibody responses and protection against influenza A virus challenge in mice

Author

Virologie, Sub Structural Biochemistry, Infectious Diseases and Immunology - Virology, Pascha, Mirte N., Ballegeer, Marlies, Roelofs, Marc C., Meuris, Leander, Albulescu, Irina C., Kuppeveld, Frank J. M. van, Hurdiss, Daniel L., Bosch, Berend-Jan, Zeev-Ben-Mordehai, Tzviya, Saelens, Xavier, Haan, Cornelis A. M. de, Virologie, Sub Structural Biochemistry, Infectious Diseases and Immunology - Virology, Pascha, Mirte N., Ballegeer, Marlies, Roelofs, Marc C., Meuris, Leander, Albulescu, Irina C., Kuppeveld, Frank J. M. van, Hurdiss, Daniel L., Bosch, Berend-Jan, Zeev-Ben-Mordehai, Tzviya, Saelens, Xavier, and Haan, Cornelis A. M. de

Published
2024

2. Unraveling dynamics of paramyxovirus-receptor interactions using nanoparticles displaying hemagglutinin-neuraminidase.

Author

Wu, Xuesheng, Goebbels, Maite, Debski-Antoniak, Oliver, Marougka, Katherine, Chao, Lemeng, Smits, Tony, Wennekes, Tom, Kuppeveld, Frank J. M. van, Vries, Erik de, and de Haan, Cornelis A. M.

Subjects
PARAINFLUENZA viruses, CELL receptors, VIRAL tropism, NEWCASTLE disease virus, ENZYME kinetics, VIRAL proteins
Abstract

Sialoglycan-binding enveloped viruses often possess receptor-destroying activity to avoid being immobilized by non-functional decoy receptors. Sialic acid (Sia)-binding paramyxoviruses contain a hemagglutinin-neuraminidase (HN) protein that possesses both Sia-binding and -cleavage activities. The multivalent, dynamic receptor interactions of paramyxovirus particles provide virion motility and are a key determinant of host tropism. However, such multivalent interactions have not been exhaustively analyzed, because such studies are complicated by the low affinity of the individual interactions and the requirement of high titer virus stocks. Moreover, the dynamics of multivalent particle-receptor interactions are difficult to predict from Michalis-Menten enzyme kinetics. Therefore, we here developed Ni-NTA nanoparticles that multivalently display recombinant soluble HN tetramers via their His tags (HN-NPs). Applying this HN-NP platform to Newcastle disease virus (NDV), we investigated using biolayer interferometry (BLI) the role of important HN residues in receptor-interactions and analyzed long-range effects between the catalytic site and the second Sia binding site (2SBS). The HN-NP system was also applicable to other paramyxoviruses. Comparative analysis of HN-NPs revealed and confirmed differences in dynamic receptor-interactions between type 1 human and murine parainfluenza viruses as well as of lab-adapted and clinical isolates of human parainfluenza virus type 3, which are likely to contribute to differences in tropism of these viruses. We propose this novel platform to be applicable to elucidate the dynamics of multivalent-receptor interactions important for host tropism and pathogenesis, particularly for difficult to grow sialoglycan-binding (paramyxo)viruses. Author summary: Multivalent dynamic interactions of sialoglycan-binding viruses, including several paramyxoviruses, are a key determinant of host tropism and pathogenesis as they allow virion motility and escape from decoy receptors to find the functional receptors at the cell surface. To facilitate analysis of these interactions by biolayer interferometry, we developed system nanoparticles that multivalently present paramyxovirus hemagglutinin-neuraminidase (HN) proteins (referred to HN-NPs), thereby omitting the need of growing high titer virus stocks. Using the HN-NP system, we performed a detailed analysis of the importance of residues in the catalytic site and the second sialic acid-binding site (2SBS) of Newcastle disease virus (NDV) for multivalent dynamic receptor interactions. Our results show that the observed phenotypes are difficult to predict from Michalis-Menten enzyme kinetics. In addition, we analyzed long-range effects between the two sites. Finally, we applied this system to compare the dynamic receptor-interactions of various parainfluenza viruses, collectively resulting in novel insights into the dynamics of multivalent-receptor interactions of paramyxoviruses. [ABSTRACT FROM AUTHOR]

Published
2024
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3. Serological Survey of Retrovirus and Coronavirus Infections, including SARS-CoV-2, in Rural Stray Cats in The Netherlands, 2020–2022

Author

Duijvestijn, Mirjam B. H. M., Schuurman, Nancy N. M. P., Vernooij, Johannes C. M., Leeuwen, Michelle A. J. M. van, Bosch, Berend-Jan, Brand, Judith M. A. van den, Wagenaar, Jaap A., Kuppeveld, Frank J. M. van, Egberink, Herman F., Verhagen, Josanne H., Klinische infectiologie en microb. lab., Virologie, and FAH Evidence based Veterinary Medicine

Subjects
Zoonosis, viral infections, feral cats, Diagnosis, Seroprevalence, serology, trap neuter return and care (TNRC), feline, feline aids, Companion animals, corona virus disease-19
Abstract

Stray cats can host (zoonotic) viral pathogens and act as a source of infection for domestic cats or humans. In this cross-sectional (sero)prevalence study, sera from 580 stray cats living in 56 different cat groups in rural areas in The Netherlands were collected from October 2020 to July 2022. These were used to investigate the prevalence of the cat-specific feline leukemia virus (FeLV, n = 580), the seroprevalence of the cat-specific feline viruses feline immunodeficiency virus (FIV, n = 580) and feline coronavirus (FCoV, n = 407), and the zoonotic virus severe acute respiratory coronavirus-2 (SARS-CoV-2, n = 407) using enzyme-linked immunosorbent assays (ELISAs). ELISA-positive results were confirmed using Western blot (FIV) or pseudovirus neutralization test (SARS-CoV-2). The FIV seroprevalence was 5.0% (95% CI (Confidence Interval) 3.4–7.1) and ranged from 0–19.0% among groups. FIV-specific antibodies were more often detected in male cats, cats ≥ 3 years and cats with reported health problems. No FeLV-positive cats were found (95% CI 0.0–0.6). The FCoV seroprevalence was 33.7% (95% CI 29.1–38.5) and ranged from 4.7–85.7% among groups. FCoV-specific antibodies were more often detected in cats ≥ 3 years, cats with reported health problems and cats living in industrial areas or countryside residences compared to cats living at holiday parks or campsites. SARS-CoV-2 antibodies against the subunit 1 (S1) and receptor binding domain (RBD) protein were detected in 2.7% (95% CI 1.4–4.8) of stray cats, but sera were negative in the pseudovirus neutralization test and therefore were considered SARS-CoV-2 suspected. Our findings suggest that rural stray cats in The Netherlands can be a source of FIV and FCoV, indicating a potential risk for transmission to other cats, while the risk for FeLV is low. However, suspected SARS-CoV-2 infections in these cats were uncommon. We found no evidence of SARS-CoV-2 cat-to-cat spread in the studied stray cat groups and consider the likelihood of spillover to humans as low.

Published
2023

4. An ACE2-blocking antibody confers broad neutralization and protection against Omicron and other SARS-CoV-2 variants of concern

Author

European Commission, German Research Foundation, Federal Ministry of Education and Research (Germany), Ministry for Science and Culture of Lower Saxony, Du, Wenjuan [0000-0002-0790-9546], Hurdiss, Daniel L. [0000-0003-3834-5808], Drabek, Dubravka [0000-0002-9781-1701], Mykytyn, Anna Z. [0000-0001-7188-6871], González-Hernandez, Mariana [0000-0001-7019-2165], Muñoz-Santos, Diego [0000-0003-0591-0874], Lamers, Mart M. [0000-0002-1431-4022], Haperen, Rien van [0000-0001-9649-011X], Li, Wentao [0000-0002-7114-762X], Drulyte, Ieva [0000-0003-1117-7699], Wang, Chunyan [0000-0002-4584-259X], Solá Gurpegui, Isabel [0000-0002-5704-1917], Armando, Federico [0000-0002-2578-4409], Beythien, Georg [0000-0002-2192-2413], Ciurkiewicz, Malgorzata [0000-0001-6277-7366], Baumgärtner, Wolfgang [0000-0001-8151-5644], Guilfoyle, Kate [0000-0001-7292-3021], Kuppeveld, Frank J. M. van [0000-0001-5800-749X], Amerongen, Geert van [0000-0002-5469-6029], Haagmans, Bart L. [0000-0001-6221-2015], Enjuanes Sánchez, Luis [0000-0002-0854-0226], Osterhaus, Albert D. M. E. [0000-0001-6535-3497], Grosveld, Frank [0000-0002-7051-4715], Du, Wenjuan, Hurdiss, Daniel L., Drabek, Dubravka, Mykytyn, Anna Z., Kaiser, Franziska K., González-Hernandez, Mariana, Muñoz-Santos, Diego, Lamers, Mart M., Haperen, Rien van, Li, Wentao, Drulyte, Ieva, Wang, Chunyan, Solá Gurpegui, Isabel, Armando, Federico, Beythien, Georg, Ciurkiewicz, Malgorzata, Baumgärtner, Wolfgang, Guilfoyle, Kate, Smits, Tony, Lee, Joline van der, Kuppeveld, Frank J. M. van, Amerongen, Geert van, Haagmans, Bart L., Enjuanes Sánchez, Luis, Osterhaus, Albert D. M. E., Grosveld, Frank, Bosch, Berend Jan, European Commission, German Research Foundation, Federal Ministry of Education and Research (Germany), Ministry for Science and Culture of Lower Saxony, Du, Wenjuan [0000-0002-0790-9546], Hurdiss, Daniel L. [0000-0003-3834-5808], Drabek, Dubravka [0000-0002-9781-1701], Mykytyn, Anna Z. [0000-0001-7188-6871], González-Hernandez, Mariana [0000-0001-7019-2165], Muñoz-Santos, Diego [0000-0003-0591-0874], Lamers, Mart M. [0000-0002-1431-4022], Haperen, Rien van [0000-0001-9649-011X], Li, Wentao [0000-0002-7114-762X], Drulyte, Ieva [0000-0003-1117-7699], Wang, Chunyan [0000-0002-4584-259X], Solá Gurpegui, Isabel [0000-0002-5704-1917], Armando, Federico [0000-0002-2578-4409], Beythien, Georg [0000-0002-2192-2413], Ciurkiewicz, Malgorzata [0000-0001-6277-7366], Baumgärtner, Wolfgang [0000-0001-8151-5644], Guilfoyle, Kate [0000-0001-7292-3021], Kuppeveld, Frank J. M. van [0000-0001-5800-749X], Amerongen, Geert van [0000-0002-5469-6029], Haagmans, Bart L. [0000-0001-6221-2015], Enjuanes Sánchez, Luis [0000-0002-0854-0226], Osterhaus, Albert D. M. E. [0000-0001-6535-3497], Grosveld, Frank [0000-0002-7051-4715], Du, Wenjuan, Hurdiss, Daniel L., Drabek, Dubravka, Mykytyn, Anna Z., Kaiser, Franziska K., González-Hernandez, Mariana, Muñoz-Santos, Diego, Lamers, Mart M., Haperen, Rien van, Li, Wentao, Drulyte, Ieva, Wang, Chunyan, Solá Gurpegui, Isabel, Armando, Federico, Beythien, Georg, Ciurkiewicz, Malgorzata, Baumgärtner, Wolfgang, Guilfoyle, Kate, Smits, Tony, Lee, Joline van der, Kuppeveld, Frank J. M. van, Amerongen, Geert van, Haagmans, Bart L., Enjuanes Sánchez, Luis, Osterhaus, Albert D. M. E., Grosveld, Frank, and Bosch, Berend Jan

Abstract

The ongoing evolution of SARS-CoV-2 has resulted in the emergence of Omicron, which displays striking immune escape potential through mutations at key antigenic sites on the spike protein. Many of these mutations localize to the spike protein ACE2 receptor-binding domain, annulling the neutralizing activity of therapeutic antibodies that were effective against other Variants of Concern (VOCs) earlier in the pandemic. Here, we identified a receptor-blocking human monoclonal antibody, 87G7, that retained potent in vitro neutralizing activity against SARS-CoV-2 variants including the Alpha, Beta, Gamma, Delta and Omicron (BA.1/BA.2) VOCs. Using cryo-electron microscopy and site-directed mutagenesis experiments, we showed that 87G7 targets a patch of hydrophobic residues in the ACE2-binding site that are highly conserved in SARS-CoV-2 variants, explaining its broad neutralization capacity. 87G7 protected mice and/or hamsters prophylactically against challenge with all current SARS-CoV-2 VOCs, and showed therapeutic activity against SARS-CoV-2 challenge in both animal models. Our findings demonstrate that 87G7 holds promise as a prophylactic or therapeutic agent for COVID-19 that is more resilient to SARS-CoV-2 antigenic diversity.

Published
2022

6. Serological Survey of Retrovirus and Coronavirus Infections, including SARS-CoV-2, in Rural Stray Cats in The Netherlands, 2020–2022

Author

Klinische infectiologie en microb. lab., Virologie, FAH Evidence based Veterinary Medicine, Infectious Diseases and Immunology - KLIF, Infectious Diseases and Immunology - Virology, Duijvestijn, Mirjam B. H. M., Schuurman, Nancy N. M. P., Vernooij, Johannes C. M., Leeuwen, Michelle A. J. M. van, Bosch, Berend-Jan, Brand, Judith M. A. van den, Wagenaar, Jaap A., Kuppeveld, Frank J. M. van, Egberink, Herman F., Verhagen, Josanne H., Klinische infectiologie en microb. lab., Virologie, FAH Evidence based Veterinary Medicine, Infectious Diseases and Immunology - KLIF, Infectious Diseases and Immunology - Virology, Duijvestijn, Mirjam B. H. M., Schuurman, Nancy N. M. P., Vernooij, Johannes C. M., Leeuwen, Michelle A. J. M. van, Bosch, Berend-Jan, Brand, Judith M. A. van den, Wagenaar, Jaap A., Kuppeveld, Frank J. M. van, Egberink, Herman F., and Verhagen, Josanne H.

Published
2023

7. A broad-spectrum macrocyclic peptide inhibitor of the SARS-CoV-2 spike protein

Author

Afd Chemical Biology and Drug Discovery, Virologie, Sub Biomol.Mass Spectrometry & Proteom., Infectious Diseases and Immunology - Virology, Thijssen, Vito, Hurdiss, Daniel L., Debski-Antoniak, Oliver J., Spence, Matthew A., Franck, Charlotte, Norman, Alexander, Aggarwal, Anupriya, Mokiem, Nadia J., Dongen, David A. A. van, Vermeir, Stein W., Liu, Minglong, Li, Wentao, Chatziandreou, Marianthi, Donselaar, Tim, Du, Wenjuan, Drulyte, Ieva, Bosch, Berend-Jan, Snijder, Joost, Turville, Stuart, Payne, Richard J., Jackson, Colin J., Kuppeveld, Frank J. M. van, Jongkees, Seino A. K., Afd Chemical Biology and Drug Discovery, Virologie, Sub Biomol.Mass Spectrometry & Proteom., Infectious Diseases and Immunology - Virology, Thijssen, Vito, Hurdiss, Daniel L., Debski-Antoniak, Oliver J., Spence, Matthew A., Franck, Charlotte, Norman, Alexander, Aggarwal, Anupriya, Mokiem, Nadia J., Dongen, David A. A. van, Vermeir, Stein W., Liu, Minglong, Li, Wentao, Chatziandreou, Marianthi, Donselaar, Tim, Du, Wenjuan, Drulyte, Ieva, Bosch, Berend-Jan, Snijder, Joost, Turville, Stuart, Payne, Richard J., Jackson, Colin J., Kuppeveld, Frank J. M. van, and Jongkees, Seino A. K.

Published
2023

8. An ACE2-blocking antibody confers broad neutralization and protection against Omicron and other SARS-CoV-2 variants

Author

European Commission, German Research Foundation, Federal Ministry of Education and Research (Germany), Ministry for Science and Culture of Lower Saxony, Du, Wenjuan, Hurdiss, Daniel L., Drabek, Dubravka, Mykytyn, Anna Z., Kaiser, Franziska K., González-Hernandez, Mariana, Muñoz-Santos, Diego, Lamers, Mart M., Haperen, Rien van, Li, Wentao, Drulyte, Ieva, Wang, Chunyan, Solá Gurpegui, Isabel, Armando, Federico, Beythien, Georg, Ciurkiewicz, Malgorzata, Baumgärtner, Wolfgang, Guilfoyle, Kate, Smits, Tony, Lee, Joline van der, Kuppeveld, Frank J. M. van, Amerongen, Geert van, Haagmans, Bart L., Enjuanes Sánchez, Luis, Osterhaus, Albert D. M. E., Grosveld, Frank, Bosch, Berend Jan, European Commission, German Research Foundation, Federal Ministry of Education and Research (Germany), Ministry for Science and Culture of Lower Saxony, Du, Wenjuan, Hurdiss, Daniel L., Drabek, Dubravka, Mykytyn, Anna Z., Kaiser, Franziska K., González-Hernandez, Mariana, Muñoz-Santos, Diego, Lamers, Mart M., Haperen, Rien van, Li, Wentao, Drulyte, Ieva, Wang, Chunyan, Solá Gurpegui, Isabel, Armando, Federico, Beythien, Georg, Ciurkiewicz, Malgorzata, Baumgärtner, Wolfgang, Guilfoyle, Kate, Smits, Tony, Lee, Joline van der, Kuppeveld, Frank J. M. van, Amerongen, Geert van, Haagmans, Bart L., Enjuanes Sánchez, Luis, Osterhaus, Albert D. M. E., Grosveld, Frank, and Bosch, Berend Jan

Abstract

The ongoing evolution of SARS-CoV-2 has resulted in the emergence of Omicron, which displays striking immune escape potential. Many of its mutations localize to the spike protein ACE2 receptor-binding domain, annulling the neutralizing activity of most therapeutic monoclonal antibodies. Here we describe a receptor-blocking human monoclonal antibody, 87G7, that retains ultrapotent neutralization against SARS-CoV-2 variants including the Alpha, Beta, Gamma, Delta and Omicron (BA.1/BA.2) Variants-of-Concern (VOCs). Structural analysis reveals that 87G7 targets a patch of hydrophobic residues in the ACE2-binding site that are highly conserved in SARS-CoV-2 variants, explaining its broad neutralization capacity. 87G7 protects mice and/or hamsters against challenge with all current SARS-CoV-2 VOCs. Our findings may aid the development of sustainable antibody-based strategies against COVID-19 that are more resilient to SARS-CoV-2 antigenic diversity.

Published
2022

9. Isolation of cross-reactive monoclonal antibodies against divergent human coronaviruses that delineate a conserved and vulnerable site on the spike protein

Author

Innovative Medicines Initiative, European Commission, European Federation of Pharmaceutical Industries and Associations, Ministerio de Economía y Competitividad (España), National Institutes of Health (US), China Scholarship Council, Bosch, Berend Jan [0000-0002-3864-232X], Wang, Chunyan, Haperen, Rien van, Gutierrez-Alvarez, Francisco J., Li, Wentao, Okba, Nisreen M. A., Albulescu, Irina, Widjaja, Ivy, Dieren, Brenda van, Fernandez-Delgado, Raúl, Solá Gurpegui, Isabel, Hurdiss, Daniel L., Daramola, Olalekan, Grosveld, Frank, Kuppeveld, Frank J. M. van, Haagmans, Bart L., Enjuanes Sánchez, Luis, Drabek, Dubravka, Bosch, Berend Jan, Innovative Medicines Initiative, European Commission, European Federation of Pharmaceutical Industries and Associations, Ministerio de Economía y Competitividad (España), National Institutes of Health (US), China Scholarship Council, Bosch, Berend Jan [0000-0002-3864-232X], Wang, Chunyan, Haperen, Rien van, Gutierrez-Alvarez, Francisco J., Li, Wentao, Okba, Nisreen M. A., Albulescu, Irina, Widjaja, Ivy, Dieren, Brenda van, Fernandez-Delgado, Raúl, Solá Gurpegui, Isabel, Hurdiss, Daniel L., Daramola, Olalekan, Grosveld, Frank, Kuppeveld, Frank J. M. van, Haagmans, Bart L., Enjuanes Sánchez, Luis, Drabek, Dubravka, and Bosch, Berend Jan

Abstract

The coronavirus spike glycoprotein, located on the virion surface, is the key mediator of cell entry. As such, it is an attractive target for the development of protective antibodies and vaccines. Here we describe two human monoclonal antibodies, 1.6C7 and 28D9, that display a remarkable cross-reactivity against distinct species from three Betacoronavirus subgenera, capable of binding the spike proteins of SARS-CoV and SARS-CoV-2, MERS-CoV and the endemic human coronavirus HCoV-OC43. Both antibodies, derived from immunized transgenic mice carrying a human immunoglobulin repertoire, blocked MERS-CoV infection in cells, whereas 28D9 also showed weak cross-neutralizing potential against HCoV-OC43, SARS-CoV and SARS-CoV-2 in a neutralization-sensitive virus pseudotyping system, but not against authentic virus. Both cross-reactive monoclonal antibodies were found to target the stem helix in the spike protein S2 fusion subunit which, in the prefusion conformation of trimeric spike, forms a surface exposed membrane-proximal helical bundle, that is antibody-accessible. We demonstrate that administration of these antibodies in mice protects from a lethal MERS-CoV challenge in both prophylactic and/or therapeutic models. Collectively, these antibodies delineate a conserved, immunogenic and vulnerabe site on the spike protein which spurs the development of broad-range diagnostic, preventive and therapeutic measures against coronaviruses.

Published
2020

10. Protective human monoclonal antibodies targeting different stages of MERS coronavirus entry

Author

Bosch, Berend Jan, Widjaja, Ivy, Wang, Chengbao, Haperen, Rien van, Dieren, Brenda van, Okba, Nisreen M. A., Stalin Raj, V., Li, Wentao, Fernandez-Delgado, Raúl, Grosveld, Frank, Kuppeveld, Frank J. M. van, Haagmans, Bart L., Enjuanes Sánchez, Luis, and Drabek, Dubravka

Abstract

Trabajo presentado en el European Congress of Virology, celebrado en Rotterdam (Países Bajos), del 28 de abril al 1 de mayo de 2019, Introduction: The Middle-East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory disease in humans with high mortality rates. Contact between humans and dromedary camels - the reservoir host of MERS-CoV - poses a continuous threat for human health. No approved antiviral drug or vaccine against MERS-CoV is currently available. Monoclonal antibodies (mAbs) targeting the spike (S) envelope glycoprotein hold promise for prophylaxis and treatment of MERS-CoV infection. The S protein displays a multi-domain architecture and functions in host-cell binding and membrane fusion via its S1 and S2 subunits, respectively. Efforts to develop antibody-based therapies have focused on neutralizing antibodies that target the receptor binding domain of the viral spike protein thereby blocking receptor binding. Aim: We aimed to develop of a set of human monoclonal antibodies that target functionally distinct domains of the MERSCoV spike protein and assess their protective efficacy in vivo. Results: From a large panel of MERS-CoV S mAbs derived from Harbour H2L2 transgenic mice encoding human immunoglobulin variable regions, eight human mAbs were generated targeting six antibody epitope groups in MERS-CoV S, suggesting the presence of at least six epitopes distributed over different domains of S1, and S2. Selected mAbs interfered with the three known entry functions of the MERS-CoV S protein: sialic acid binding, receptor binding or membrane fusion. Prophylactic administration of these mAbs protected mice from lethal MERSCoV challenge resulting in 40-100% survival rates. Complete protection from mortality was shown for antibodies that block receptor binding, but also for antibodies that inhibit membrane fusion regardless of their limited in-vitro neutralization capacity. Conclusion: The arsenal of protective antibodies that bind to and functionally inhibit the activity of multiple spike protein domains offers new ways to gain humoral protection against the emerging MERS coronavirus.

Published
2019

11. Differential receptor use of Enterovirus D-68 strains in human airway epithelial cultures

Author

Adithya Sridhar, Karelehto, Eveliina, Baggen, Jim, Linden, Lonneke Van Der, Meijer, Adam, Kuppeveld, Frank J. M Van, Dasja Pajkrt, and Wolthers, Katja C.

Subjects
ComputingMethodologies_SIMULATIONANDMODELING, Data_FILES, Biological Sciences, GeneralLiterature_MISCELLANEOUS, ComputingMethodologies_COMPUTERGRAPHICS
Abstract

submitted for positive strand meeting 2019. File available on request.

Published
2019
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12. Towards a solution to MERS: Protective human monoclonal antibodies targeting different domains and functions of the MERS-coronavirus spike glycoprotein

Author

Widjaja, Ivy, Wang, Chengbao, Haperen, Rien van, Gutierrez-Alvarez, Francisco J., Dieren, Brenda van, Okba, Nisreen M. A., Stalin Raj, V., Li, Wentao, Fernandez-Delgado, Raúl, Grosveld, Frank, Kuppeveld, Frank J. M. van, Haagmans, Bart L., Enjuanes Sánchez, Luis, Drabek, Dubravka, Bosch, Berend Jan, Widjaja, Ivy, Wang, Chengbao, Haperen, Rien van, Gutierrez-Alvarez, Francisco J., Dieren, Brenda van, Okba, Nisreen M. A., Stalin Raj, V., Li, Wentao, Fernandez-Delgado, Raúl, Grosveld, Frank, Kuppeveld, Frank J. M. van, Haagmans, Bart L., Enjuanes Sánchez, Luis, Drabek, Dubravka, and Bosch, Berend Jan

Abstract

The Middle-East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic virus that causes severe and often fatal respiratory disease in humans. Efforts to develop antibody-based therapies have mainly focused on neutralizing antibodies that target the receptor binding domain of the viral spike protein thereby blocking receptor binding. We developed a set of human monoclonal antibodies that target functionally distinct domains of the MERS-CoV spike protein. These antibodies belong to six distinct epitope groups and interfere with the three critical entry functions of the MERS-CoV spike protein: sialic acid binding, receptor binding and membrane fusion. Passive immunization with potently as well as with poorly neutralizing antibodies protected mice from lethal MERS-CoV challenge. Collectively, these antibodies offer new ways to gain humoral protection in humans against the emerging MERS-CoV by targeting different spike protein epitopes and functions.

Published
2019

13. Towards a solution to MERS: protective human monoclonal antibodies targeting different domains and functions of the MERS-coronavirus spike glycoprotein

Author

European Commission, Innovative Medicines Initiative, European Federation of Pharmaceutical Industries and Associations, Ministerio de Economía y Competitividad (España), National Institutes of Health (US), China Scholarship Council, Widjaja, Ivy, Wang, Chengbao, Haperen, Rien van, Gutierrez-Alvarez, Francisco J., Dieren, Brenda van, Okba, Nisreen M. A., Stalin Raj, V., Li, Wentao, Fernandez-Delgado, Raúl, Grosveld, Frank, Kuppeveld, Frank J. M. van, Haagmans, Bart L., Enjuanes Sánchez, Luis, Drabek, Dubravka, Bosch, Berend Jan, European Commission, Innovative Medicines Initiative, European Federation of Pharmaceutical Industries and Associations, Ministerio de Economía y Competitividad (España), National Institutes of Health (US), China Scholarship Council, Widjaja, Ivy, Wang, Chengbao, Haperen, Rien van, Gutierrez-Alvarez, Francisco J., Dieren, Brenda van, Okba, Nisreen M. A., Stalin Raj, V., Li, Wentao, Fernandez-Delgado, Raúl, Grosveld, Frank, Kuppeveld, Frank J. M. van, Haagmans, Bart L., Enjuanes Sánchez, Luis, Drabek, Dubravka, and Bosch, Berend Jan

Abstract

The Middle-East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic virus that causes severe and often fatal respiratory disease in humans. Efforts to develop antibody-based therapies have focused on neutralizing antibodies that target the receptor binding domain of the viral spike protein thereby blocking receptor binding. Here, we developed a set of human monoclonal antibodies that target functionally distinct domains of the MERS-CoV spike protein. These antibodies belong to six distinct epitope groups and interfere with the three critical entry functions of the MERS-CoV spike protein: sialic acid binding, receptor binding and membrane fusion. Passive immunization with potently as well as with poorly neutralizing antibodies protected mice from lethal MERS-CoV challenge. Collectively, these antibodies offer new ways to gain humoral protection in humans against the emerging MERS-CoV by targeting different spike protein epitopes and functions.

Published
2019

14. Middle East respiratory coronavirus accessory protein 4a inhibits PKR-mediated antiviral stress responses

Author

Netherlands Organization for Scientific Research, Rabouw, Huib H., Langereis, Martijn A., Knaap, Robert C., Dalebout, Tim J., Cantón, Javier, Solá Gurpegui, Isabel, Enjuanes Sánchez, Luis, Bredenbeek, Peter J., Kikkert, Marjolein, Groot, Raoul J. de, Kuppeveld, Frank J. M. van, Netherlands Organization for Scientific Research, Rabouw, Huib H., Langereis, Martijn A., Knaap, Robert C., Dalebout, Tim J., Cantón, Javier, Solá Gurpegui, Isabel, Enjuanes Sánchez, Luis, Bredenbeek, Peter J., Kikkert, Marjolein, Groot, Raoul J. de, and Kuppeveld, Frank J. M. van

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory infections that can be life-threatening. To establish an infection and spread, MERS-CoV, like most other viruses, must navigate through an intricate network of antiviral host responses. Besides the well-known type I interferon (IFN-alpha/beta) response, the protein kinase R (PKR)-mediated stress response is being recognized as an important innate response pathway.

Published
2016

15. An ACE2-blocking antibody confers broad neutralization and protection against Omicron and other SARS-CoV-2 variants of concern

Author

Du, Wenjuan, Hurdiss, Daniel L, Drabek, Dubravka, Mykytyn, Anna Z, Kaiser, Franziska K, González-Hernández, Mariana, Muñoz-Santos, Diego, Lamers, Mart M, van Haperen, Rien, Li, Wentao, Drulyte, Ieva, Wang, Chunyan, Sola, Isabel, Armando, Federico, Beythien, Georg, Ciurkiewicz, Malgorzata, Baumgärtner, Wolfgang, Guilfoyle, Kate, Smits, Tony, van der Lee, Joline, van Kuppeveld, Frank J M, van Amerongen, Geert, Haagmans, Bart L, Enjuanes, Luis, Osterhaus, Albert D M E, Grosveld, Frank, Bosch, Berend-Jan, Virologie, dI&I I&I-1, Bedrijfsvoering, European Commission, German Research Foundation, Federal Ministry of Education and Research (Germany), Ministry for Science and Culture of Lower Saxony, Du, Wenjuan [0000-0002-0790-9546], Hurdiss, Daniel L. [0000-0003-3834-5808], Drabek, Dubravka [0000-0002-9781-1701], Mykytyn, Anna Z. [0000-0001-7188-6871], González-Hernandez, Mariana [0000-0001-7019-2165], Muñoz-Santos, Diego [0000-0003-0591-0874], Lamers, Mart M. [0000-0002-1431-4022], Haperen, Rien van [0000-0001-9649-011X], Li, Wentao [0000-0002-7114-762X], Drulyte, Ieva [0000-0003-1117-7699], Wang, Chunyan [0000-0002-4584-259X], Solá Gurpegui, Isabel [0000-0002-5704-1917], Armando, Federico [0000-0002-2578-4409], Beythien, Georg [0000-0002-2192-2413], Ciurkiewicz, Malgorzata [0000-0001-6277-7366], Baumgärtner, Wolfgang [0000-0001-8151-5644], Guilfoyle, Kate [0000-0001-7292-3021], Kuppeveld, Frank J. M. van [0000-0001-5800-749X], Amerongen, Geert van [0000-0002-5469-6029], Haagmans, Bart L. [0000-0001-6221-2015], Enjuanes Sánchez, Luis [0000-0002-0854-0226], Osterhaus, Albert D. M. E. [0000-0001-6535-3497], Grosveld, Frank [0000-0002-7051-4715], Virologie, dI&I I&I-1, Bedrijfsvoering, Cell biology, Virology, Du, Wenjuan, Hurdiss, Daniel L., Drabek, Dubravka, Mykytyn, Anna Z., González-Hernandez, Mariana, Muñoz-Santos, Diego, Lamers, Mart M., Haperen, Rien van, Li, Wentao, Drulyte, Ieva, Wang, Chunyan, Solá Gurpegui, Isabel, Armando, Federico, Beythien, Georg, Ciurkiewicz, Malgorzata, Baumgärtner, Wolfgang, Guilfoyle, Kate, Kuppeveld, Frank J. M. van, Amerongen, Geert van, Haagmans, Bart L., Enjuanes Sánchez, Luis, Osterhaus, Albert D. M. E., and Grosveld, Frank

Subjects
Membrane Glycoproteins, SARS-CoV-2, Cryoelectron Microscopy, Immunology, General Medicine, Refinement, Antibodies, Neutralizing, COVID-19 Drug Treatment, Mice, Viral Envelope Proteins, Neutralization Tests, Spike Glycoprotein, Coronavirus, Validation, Animals, Humans, Immunology and Allergy, Angiotensin-Converting Enzyme 2, Model, Visualization
Abstract

The ongoing evolution of SARS-CoV-2 has resulted in the emergence of Omicron, which displays striking immune escape potential through mutations at key antigenic sites on the spike protein. Many of these mutations localize to the spike protein ACE2 receptor-binding domain, annulling the neutralizing activity of therapeutic antibodies that were effective against other Variants of Concern (VOCs) earlier in the pandemic. Here, we identified a receptor-blocking human monoclonal antibody, 87G7, that retained potent in vitro neutralizing activity against SARS-CoV-2 variants including the Alpha, Beta, Gamma, Delta and Omicron (BA.1/BA.2) VOCs. Using cryo-electron microscopy and site-directed mutagenesis experiments, we showed that 87G7 targets a patch of hydrophobic residues in the ACE2-binding site that are highly conserved in SARS-CoV-2 variants, explaining its broad neutralization capacity. 87G7 protected mice and/or hamsters prophylactically against challenge with all current SARS-CoV-2 VOCs, and showed therapeutic activity against SARS-CoV-2 challenge in both animal models. Our findings demonstrate that 87G7 holds promise as a prophylactic or therapeutic agent for COVID-19 that is more resilient to SARS-CoV-2 antigenic diversity., The MANCO project has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 101003651). This work made use of the Dutch national e-infrastructure with the support of the SURF Cooperative using grant no. EINF-2453. This research was funded by the Deutsche Forschungsgemeinschaft (DFG; German Research Foundation) -398066876/GRK 2485/1; BMBF (Federal Ministry of Education and Research) project entitled RAPID (Risk assessment in re-pandemic respiratory infectious diseases), 01KI1723G, Ministry of Science and Culture of Lower Saxony in Germany (14 - 76103-184 CORONA-15/20)

Published
2022

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