• Open Access

Early neutralizing IgG response to Chikungunya virus in infected patients targets a dominant linear epitope on the E2 glycoprotein

Authors

  • Yiu-Wing Kam,

    1. Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore
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    • These authors contributed equally to this work.

  • Fok-Moon Lum,

    1. Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore
    2. Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
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    • These authors contributed equally to this work.

  • Teck-Hui Teo,

    1. Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore
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    • These authors contributed equally to this work.

  • Wendy W. L. Lee,

    1. Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore
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  • Diane Simarmata,

    1. Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore
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  • Sumitro Harjanto,

    1. Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore
    2. Data Mining Department, Institute for Infocomm Research, A*STAR Fusionopolis, Singapore
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  • Chong-Long Chua,

    1. Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
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  • Yoke-Fun Chan,

    1. Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
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  • Jin-Kiat Wee,

    1. Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore
    2. Data Mining Department, Institute for Infocomm Research, A*STAR Fusionopolis, Singapore
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  • Angela Chow,

    1. Communicable Diseases Centre, Tan Tock Seng Hospital, Singapore
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  • Raymond T. P. Lin,

    1. National Public Health Laboratory, Communicable Diseases Division, Ministry of Health, Singapore
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  • Yee-Sin Leo,

    1. Communicable Diseases Centre, Tan Tock Seng Hospital, Singapore
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  • Roger Le Grand,

    1. Division of ImmunoVirology (SIV), Institute of Emerging Diseases and Innovative Therapies (IMETI), CEA, Fontenay-aux-Roses, France
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  • I-Ching Sam,

    1. Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
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  • Joo-Chuan Tong,

    1. Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
    2. Data Mining Department, Institute for Infocomm Research, A*STAR Fusionopolis, Singapore
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  • Pierre Roques,

    1. Division of ImmunoVirology (SIV), Institute of Emerging Diseases and Innovative Therapies (IMETI), CEA, Fontenay-aux-Roses, France
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  • Karl-Heinz Wiesmüller,

    1. EMC Microcollections GmbH, Tübingen, Germany
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  • Laurent Rénia,

    1. Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore
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  • Olaf Rötzschke,

    1. Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore
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  • Lisa F. P. Ng

    Corresponding author
    1. Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore
    2. Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
    3. Present address: Laboratory of Chikungunya Virus Immunity, Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore
    • Tel: +65 64070028; Fax: +65 64642057

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Abstract

Chikungunya virus (CHIKV) and related arboviruses have been responsible for large epidemic outbreaks with serious economic and social impact. The immune mechanisms, which control viral multiplication and dissemination, are not yet known. Here, we studied the antibody response against the CHIKV surface antigens in infected patients. With plasma samples obtained during the early convalescent phase, we showed that the naturally-acquired IgG response is dominated by IgG3 antibodies specific mostly for a single linear epitope ‘E2EP3’. E2EP3 is located at the N-terminus of the E2 glycoprotein and prominently exposed on the viral envelope. E2EP3-specific antibodies are neutralizing and their removal from the plasma reduced the CHIKV-specific antibody titer by up to 80%. Screening of E2EP3 across different patient cohorts and in non-human primates demonstrated the value of this epitope as a good serology detection marker for CHIKV infection already at an early stage. Mice vaccinated by E2EP3 peptides were protected against CHIKV with reduced viremia and joint inflammation, providing a pre-clinical basis for the design of effective vaccine against arthralgia-inducing CHIKV and other alphaviruses.

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