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Chikungunya Virus Envelope-Specific Human Monoclonal Antibodies with Broad Neutralization Potency

Lucile Warter, Chia Yin Lee, Rekha Thiagarajan, Marc Grandadam, Serge Lebecque, Raymond T. P. Lin, Sebastien Bertin-Maghit, Lisa F. P. Ng, Jean-Pierre Abastado, Philippe Desprès, Cheng-I Wang and Alessandra Nardin
J Immunol January 28, 2011, 1003139; DOI: https://doi.org/10.4049/jimmunol.1003139
Lucile Warter
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Chia Yin Lee
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Rekha Thiagarajan
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Marc Grandadam
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Serge Lebecque
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Raymond T. P. Lin
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Sebastien Bertin-Maghit
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Lisa F. P. Ng
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Jean-Pierre Abastado
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Philippe Desprès
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Cheng-I Wang
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Alessandra Nardin
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Abstract

Chikungunya virus (CHIKV) is an alphavirus responsible for numerous epidemics in Africa and Asia. Infection by CHIKV is often characterized by long-lasting, incapacitating arthritis, and some fatal cases have been described among elderly and newborns. Currently, there is no available vaccine or specific treatment against CHIKV. Blood B cells from a donor with history of CHIKV infection were activated, immortalized, amplified, and cloned. Two human mAbs against CHIKV, 5F10 and 8B10, were identified, sequenced, and expressed in recombinant form for characterization. In a plaque reduction neutralization test, 5F10 and 8B10 show mean IC50 of 72 and 46 ng/ml, respectively. Moreover, both mAbs lead to a strong decrease in extracellular spreading of infectious viral particles from infected to uninfected cells. Importantly, the mAbs neutralize different CHIKV isolates from Singapore, Africa, and Indonesia, as well as O’nyong-nyong virus, but do not recognize other alphaviruses tested. Both mAbs are specific for the CHIKV envelope: 5F10 binds to the E2 glycoprotein ectodomain and 8B10 to E1 and/or E2. In conclusion, these two unique human mAbs strongly, broadly, and specifically neutralize CHIKV infection in vitro and might become possible therapeutic tools against CHIKV infection, especially in individuals at risk for severe disease. Importantly, these mAbs will also represent precious tools for future studies on host–pathogen interactions and the rational design of vaccines against CHIKV.

Footnotes

  • This work was supported by the Biomedical Research Council, Agency for Science, Technology and Research, and the Institut Pasteur’s research and development fund (to P.D.).

  • Received September 21, 2010.
  • Accepted December 15, 2010.
  • Copyright © 2011 by The American Association of Immunologists, Inc.
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The Journal of Immunology: 203 (12)
The Journal of Immunology
Vol. 203, Issue 12
15 Dec 2019
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Chikungunya Virus Envelope-Specific Human Monoclonal Antibodies with Broad Neutralization Potency
Lucile Warter, Chia Yin Lee, Rekha Thiagarajan, Marc Grandadam, Serge Lebecque, Raymond T. P. Lin, Sebastien Bertin-Maghit, Lisa F. P. Ng, Jean-Pierre Abastado, Philippe Desprès, Cheng-I Wang, Alessandra Nardin
The Journal of Immunology January 28, 2011, 1003139; DOI: 10.4049/jimmunol.1003139

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Chikungunya Virus Envelope-Specific Human Monoclonal Antibodies with Broad Neutralization Potency
Lucile Warter, Chia Yin Lee, Rekha Thiagarajan, Marc Grandadam, Serge Lebecque, Raymond T. P. Lin, Sebastien Bertin-Maghit, Lisa F. P. Ng, Jean-Pierre Abastado, Philippe Desprès, Cheng-I Wang, Alessandra Nardin
The Journal of Immunology January 28, 2011, 1003139; DOI: 10.4049/jimmunol.1003139
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Print ISSN 0022-1767        Online ISSN 1550-6606