title: Early neutralizing IgG response to Chikungunya virus in infected patients targets a dominant linear epitope on the E2 glycoprotein.
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.
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore.
authors.forename: Yiu-Wing
authors.initials: YW
authors.lastname: Kam
authors.forename: Fok-Moon
authors.initials: FM
authors.lastname: Lum
authors.forename: Teck-Hui
authors.initials: TH
authors.lastname: Teo
authors.forename: Wendy W L
authors.initials: WW
authors.lastname: Lee
authors.forename: Diane
authors.initials: D
authors.lastname: Simarmata
authors.forename: Sumitro
authors.initials: S
authors.lastname: Harjanto
authors.forename: Chong-Long
authors.initials: CL
authors.lastname: Chua
authors.forename: Yoke-Fun
authors.initials: YF
authors.lastname: Chan
authors.forename: Jin-Kiat
authors.initials: JK
authors.lastname: Wee
authors.forename: Angela
authors.initials: A
authors.lastname: Chow
authors.forename: Raymond T P
authors.initials: RT
authors.lastname: Lin
authors.forename: Yee-Sin
authors.initials: YS
authors.lastname: Leo
authors.forename: Roger
authors.initials: R
authors.lastname: Le Grand
authors.forename: I-Ching
authors.initials: IC
authors.lastname: Sam
authors.forename: Joo-Chuan
authors.initials: JC
authors.lastname: Tong
authors.forename: Pierre
authors.initials: P
authors.lastname: Roques
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Wiesmüller
authors.forename: Laurent
authors.initials: L
authors.lastname: Rénia
authors.forename: Olaf
authors.initials: O
authors.lastname: Rötzschke
authors.forename: Lisa F P
authors.initials: LF
authors.lastname: Ng
mesh_terms: D018354:Alphavirus Infections / Q000097:blood / Q000276:immunology* / Q000517:prevention & control; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology*; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D000917:Antibody Formation; D065632:Chikungunya Fever; D002646:Chikungunya virus / Q000276:immunology*; D000939:Epitopes / Q000097:blood / Q000737:chemistry / Q000276:immunology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D008253:Macaca mulatta; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D014611:Vaccination; D014759:Viral Envelope Proteins / Q000097:blood / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology / Q000627:therapeutic use
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000939:Epitopes; D007074:Immunoglobulin G; D014759:Viral Envelope Proteins; D014765:Viral Vaccines