Early neutralizing IgG response to Chikungunya virus in infected patients targets a dominant linear epitope on the E2 glycoprotein
| Autor: | Roger Le Grand, Lisa F. P. Ng, C.L. Chua, Angela Chow, Jin‐Kiat Wee, Teck-Hui Teo, Olaf Rötzschke, Pierre Roques, Laurent Rénia, Fok-Moon Lum, Diane Simarmata, Sumitro Harjanto, Raymond T. P. Lin, Yiu-Wing Kam, Yee Sin Leo, Yoke Fun Chan, Wendy W. L. Lee, Joo Chuan Tong, Karl-Heinz Wiesmüller, I-Ching Sam |
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| Rok vydání: | 2011 |
| Předmět: |
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Molecular pre-clinical vaccine 030231 tropical medicine CHIKV linear neutralization epitopes medicine.disease_cause Antibodies Viral Virus Immunoglobulin G Epitope Serology 03 medical and health sciences Epitopes Mice 0302 clinical medicine Viral Envelope Proteins medicine Animals Humans Chikungunya 030304 developmental biology 0303 health sciences biology Linear epitope Alphavirus Infections Vaccination Antibody titer virus diseases Viral Vaccines protection Virology Antibodies Neutralizing Macaca mulatta 3. Good health Mice Inbred C57BL Immunology Antibody Formation biology.protein serology maker Molecular Medicine Chikungunya Fever Female Antibody Chikungunya virus Research Article |
| Zdroj: | EMBO Molecular Medicine EMBO Molecular Medicine; Vol 4 |
| ISSN: | 1757-4684 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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