Identification of a novel infection-enhancing epitope on dengue prM using a dengue cross-reacting monoclonal antibody

BMC Microbiology

Research Article

Li-Fang Jiang¹  Jun-Jie Feng¹  Zhi-Zhun Yu¹  Dan-Yun Fang¹  Ya-Yan Luo¹  Gu-Cheng Zeng¹  Jun-Mei Zhou¹  Hui-Jun Yan¹ 

[1] Key Laboratory for Tropic Diseases Control, Ministry of Education of China, Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, China;

关键词: Dengue virus;    prM protein;    Epitope;    Phage display peptide library;    Antibody-dependent enhancement;   

DOI  :  10.1186/1471-2180-13-194

 received in 2013-04-24, accepted in 2013-08-26,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundDengue virus (DENV) infection is the most important arthropod- borne viral disease in human, but antiviral therapy and approved vaccines remain unavailable due to antibody-dependent enhancement (ADE) phenomenon. Many studies showed that pre-membrane (prM)-specific antibodies do not efficiently neutralize DENV infection but potently promote ADE infection. However, most of the binding epitopes of these antibodies remain unknown.ResultsIn the present study, we characterized a DENV cross-reactive monoclonal antibody (mAb), 4D10, that neutralized poorly but potently enhanced infection of four standard DENV serotypes and immature DENV (imDENV) over a broad range of concentration. In addition, the epitope of 4D10 was successfully mapped to amino acid residues 14 to18 of DENV1-4 prM protein using a phage-displayed peptide library and comprehensive bioinformatics analysis. We found that the epitope was DENV serocomplex cross-reactive and showed to be highly immunogenic in Balb/c mice. Furthermore, antibody against epitope peptide PL10, like 4D10, showed broad cross-reactivity and weak neutralizing activtity with four standard DENV serotypes and imDENV but significantly promoted ADE infection. These results suggested 4D10 and anti-PL10 sera were infection-enhancing antibodies and PL10 was infection-enhancing epitope.ConclusionsWe mapped the epitope of 4D10 to amino acid residues 14 to18 of DENV1-4 prM and found that this epitope was infection-enhancing. These findings may provide significant implications for future vaccine design and facilitate understanding the pathogenesis of DENV infection.

【 授权许可】

Unknown   
© Luo et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.