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Research Article

Human Monoclonal Antibody Combination against SARS Coronavirus: Synergy and Coverage of Escape Mutants

  • Jan ter Meulen equal contributor mail,

    equal contributor Contributed equally to this work with: Jan ter Meulen, Edward N van den Brink

    To whom correspondence should be addressed. E-mail: j.termeulen@crucell.com

    Affiliation: Crucell Holland B.V., Leiden, Netherlands

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  • Edward N van den Brink equal contributor,

    equal contributor Contributed equally to this work with: Jan ter Meulen, Edward N van den Brink

    Affiliation: Crucell Holland B.V., Leiden, Netherlands

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  • Leo L. M Poon,

    Affiliation: Department of Microbiology, The University of Hong Kong, Queen Mary Hospital, Hong Kong Special Administrative Region of the People's Republic of China

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  • Wilfred E Marissen,

    Affiliation: Crucell Holland B.V., Leiden, Netherlands

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  • Cynthia S. W Leung,

    Affiliation: Department of Microbiology, The University of Hong Kong, Queen Mary Hospital, Hong Kong Special Administrative Region of the People's Republic of China

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  • Freek Cox,

    Affiliation: Crucell Holland B.V., Leiden, Netherlands

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  • Chung Y Cheung,

    Affiliation: Department of Microbiology, The University of Hong Kong, Queen Mary Hospital, Hong Kong Special Administrative Region of the People's Republic of China

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  • Arjen Q Bakker,

    Affiliation: Crucell Holland B.V., Leiden, Netherlands

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  • Johannes A Bogaards,

    Affiliation: Crucell Holland B.V., Leiden, Netherlands

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  • Els van Deventer,

    Affiliation: Crucell Holland B.V., Leiden, Netherlands

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  • Wolfgang Preiser,

    Affiliation: Institute for Medical Virology, Johann Wolfgang Goethe University, Frankfurt am Main, Germany

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  • Hans Wilhelm Doerr,

    Affiliation: Institute for Medical Virology, Johann Wolfgang Goethe University, Frankfurt am Main, Germany

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  • Vincent T Chow,

    Affiliation: Department of Microbiology, Yong Loo Lin School Faculty of Medicine, National University of Singapore, Singapore

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  • John de Kruif,

    Affiliation: Crucell Holland B.V., Leiden, Netherlands

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  • Joseph S. M Peiris,

    Affiliation: Department of Microbiology, The University of Hong Kong, Queen Mary Hospital, Hong Kong Special Administrative Region of the People's Republic of China

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  • Jaap Goudsmit

    Affiliation: Crucell Holland B.V., Leiden, Netherlands

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  • Published: July 04, 2006
  • DOI: 10.1371/journal.pmed.0030237

About the Authors

Jan ter Meulen, Edward N van den Brink, Wilfred E Marissen, Freek Cox, Arjen Q Bakker, Johannes A Bogaards, Els van Deventer, John de Kruif, Jaap Goudsmit
Crucell Holland B.V., Leiden, Netherlands
Leo L. M Poon, Cynthia S. W Leung, Chung Y Cheung, Joseph S. M Peiris
Department of Microbiology, The University of Hong Kong, Queen Mary Hospital, Hong Kong Special Administrative Region of the People's Republic of China
Wolfgang Preiser, Hans Wilhelm Doerr
Institute for Medical Virology, Johann Wolfgang Goethe University, Frankfurt am Main, Germany
Vincent T Chow
Department of Microbiology, Yong Loo Lin School Faculty of Medicine, National University of Singapore, Singapore

Corresponding Author

Email: j.termeulen@crucell.com

Competing Interests

Part of the direct costs (labor, cell culture material) of the SARS-CoV neutralization experiments performed with the monoclonal antibodies at the Universities of Frankfurt and Hong Kong were reimbursed by Crucell Holland BV. Crucell was involved in the design, the analysis of the data, and the publication decision. However, Crucell was at no time involved in performing experiments with live virus. JtM, ENvdB, WEM, FC, AQB, JAB, EvD, JdK, and JG are employees of Crucell Holland BV.

Author Contributions

JtM, ENvdB, JdK, and JG designed the study. AQB built the immune library, and ENvdB and FC isolated mAb CR3022. WP and HWD designed and performed virus neutralization experiments. JAB designed and analyzed the synergy experiments, which were performed by CSWL, CYC, and WP. ENvdB and FC constructed the recombinant spike fragments and tested their binding to mAbs. EvD designed and performed Biacore experiments. LLMP, WEM, CSWL, CYC, and JSMP designed and performed the rescue of the neutralization escape viruses and macrophage infection assays. VTC recruited the patient whose lymphocytes were used for library construction to generate the monoclonal antibody CR3022. JtM, ENvdB, LLMP, WEM, CYC, AQB, JAB, EvD, WP, HWD, VTC, JdK, JSMP, and JG analyzed and interpreted the data and contributed to writing the paper.