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

EMBO Molecular Medicine

Yiu-Wing Kam²  Fok-Moon Lum²  Teck-Hui Teo²  Wendy W. L. Lee²  Diane Simarmata²  Sumitro Harjanto²  Chong-Long Chua⁴  Yoke-Fun Chan⁴  Jin-Kiat Wee²  Angela Chow⁵  Raymond T. P. Lin⁶  Yee-Sin Leo⁵  Roger Le Grand³  I-Ching Sam⁴  Joo-Chuan Tong¹  Pierre Roques³  Karl-Heinz Wiesmüller⁷  Laurent Rénia²  Olaf Rötzschke² 

[1] Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore;Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore;Division of ImmunoVirology (SIV), Institute of Emerging Diseases and Innovative Therapies (IMETI), CEA, Fontenay-aux-Roses, France;Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia;Communicable Diseases Centre, Tan Tock Seng Hospital, Singapore;National Public Health Laboratory, Communicable Diseases Division, Ministry of Health, Singapore;EMC Microcollections GmbH, Tübingen, Germany

关键词: CHIKV;    linear neutralization epitopes;    pre‐clinical vaccine;    protection;    serology maker;   

DOI  :  10.1002/emmm.201200213

来源: Wiley

【 摘 要 】

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.

【 授权许可】

Unknown   
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