Open Access Open Badges Research article

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

Ya-Yan Luo, Jun-Jie Feng, Jun-Mei Zhou, Zhi-Zhun Yu, Dan-Yun Fang, Hui-Jun Yan, Gu-Cheng Zeng and Li-Fang Jiang*

Author affiliations

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

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Citation and License

BMC Microbiology 2013, 13:194  doi:10.1186/1471-2180-13-194

Published: 29 August 2013



Dengue 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.


In 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.


We 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.

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