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

Kam, Y.W. and Lum, F.M. and Teo, T.H. and Lee, W.W.L. and Simarmata, D. and Harjanto, S. and Chua, C.L. and Chan, Y.F. and Wee, J.K. and Chow, A. and Lin, R.T.P. and Leo, Y.S. and Le Grand, R. and Sam, I.C. and Tong, J.C. and Roques, P. and Wiesmuller, K.H. and Renia, L. and Rotzschke, O. and Ng, L.F.P. (2012) Early neutralizing IgG response to Chikungunya virus in infected patients targets a dominant linear epitope on the E2 glycoprotein. Embo Molecular Medicine, 4 (4). pp. 330-343. ISSN 1757-4676

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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.

Item Type: Article
Additional Information: Times Cited: 4 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 Grand, Roger Sam, I-Ching Tong, Joo-Chuan Roques, Pierre Wiesmueller, Karl-Heinz Renia, Laurent Roetzschke, Olaf Ng, Lisa F. P.
Uncontrolled Keywords: CHIKV; linear neutralization epitopes; pre-clinical vaccine; protection; serology maker
Subjects: R Medicine
Divisions: Faculty of Medicine
Depositing User: Ms azrahani halim
Date Deposited: 12 Jul 2013 03:45
Last Modified: 11 Dec 2013 06:33
URI: http://eprints.um.edu.my/id/eprint/7271

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