title: Identification of a novel infection-enhancing epitope on dengue prM using a dengue cross-reacting monoclonal antibody.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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. jianglf@mail.sysu.edu.cn.
authors.forename: Ya-Yan
authors.initials: YY
authors.lastname: Luo
authors.forename: Jun-Jie
authors.initials: JJ
authors.lastname: Feng
authors.forename: Jun-Mei
authors.initials: JM
authors.lastname: Zhou
authors.forename: Zhi-Zhun
authors.initials: ZZ
authors.lastname: Yu
authors.forename: Dan-Yun
authors.initials: DY
authors.lastname: Fang
authors.forename: Hui-Jun
authors.initials: HJ
authors.lastname: Yan
authors.forename: Gu-Cheng
authors.initials: GC
authors.lastname: Zeng
authors.forename: Li-Fang
authors.initials: LF
authors.lastname: Jiang
mesh_terms: D000328:Adult; D000818:Animals; D019138:Antibodies, Blocking / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology*; D019295:Computational Biology; D003429:Cross Reactions; D003715:Dengue; D003716:Dengue Virus / Q000276:immunology*; D018604:Epitope Mapping; D000939:Epitopes / Q000276:immunology*; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D019151:Peptide Library; D014759:Viral Envelope Proteins / Q000276:immunology*
chemical_list: D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000956:Antigens, Viral; D000939:Epitopes; D019151:Peptide Library; D014759:Viral Envelope Proteins; C074932:prM protein, Flavivirus