Early neutralizing IgG response to Chikungunya virus in infected patients targets a dominant linear epitope on the E2 glycoprotein
Autor(es): Kam Yiu-Wing, Lum Fok-Moon, Teo Teck-Hui, Lee Wendy W L, Simarmata Diane, Harjanto Sumitro, Chua Chong-Long, Chan Yoke-Fun, Wee Jin-Kiat, Chow Angela, Lin Raymond T P, Leo Yee-Sin, Le Gr- Roger, Sam I-Ching, Tong Joo-Chuan, Roques Pierre, Wiesmüller Karl-Heinz, Rénia Laurent, Rötzschke Olaf, Ng Lisa F P
Resumo: Chikungunya virus (CHIKV) - related arboviruses have been responsible for large epidemic outbreaks with serious economic - social impact. The immune mechanisms, which control viral multiplication - 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 - prominently exposed on the viral envelope. E2EP3-specific antibodies are neutralizing - their removal from the plasma reduced the CHIKV-specific antibody titer by up to 80%. Screening of E2EP3 across different patient cohorts - 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 - joint inflammation, providing a pre-clinical basis for the design of effective vaccine against arthralgia-inducing CHIKV - other alphaviruses.
Imprenta: EMBO Molecular Medicine, v. 4, n. 4, p. 330-343, 2012
Identificador do objeto digital: 10.1002/emmm.201200213
Descritores: Chikungunya virus - Arbovirus ; Chikungunya virus - Immune response ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Proteins ; Chikungunya virus - Antibodies ; Chikungunya virus - Immune response ; Chikungunya virus - Inflammation ; Chikungunya virus - Serology ; Chikungunya virus - Viral infections ; Chikungunya virus - Serology ; Chikungunya Virus - Virus ; Chikungunya virus - Molecular screening ; Chikungunya virus - Vaccine ; Chikungunya virus - Chikungunya fever ; Chikungunya virus - Epidemic ; Chikungunya virus - Immunology ; Chikungunya virus - Public health
Data de publicação: 2012
