title: Comprehensive mapping infection-enhancing epitopes of dengue pr protein using polyclonal antibody against prM.
abstract: Dengue vaccine development is considered a global public health priority, but the antibody-dependent enhancement (ADE) issues have critically restricted vaccine development. Recent findings have demonstrated that pre-membrane (prM) protein was involved in dengue virus (DENV) infection enhancement. Although the importance of prM antibodies have been well characterized, only a few epitopes in DENV prM protein have ever been identified. In this study, we screened five potential linear epitopes located at positions pr1 (1-16aa), pr3 (13-28aa), pr4 (19-34aa), pr9 (49-64aa), and pr10 (55-70aa) in pr protein using peptide scanning and comprehensive bioinformatics analysis. Then, we found that only pr4 (19-34aa) could elicit high-titer antibodies in Balb/c mice, and this epitope could react with sera from DENV2-infected patients, suggesting that specific antibodies against epitope peptide pr4 were elicited in both DENV-infected mice and human. In addition, our data demonstrated that anti-pr4 sera showed limited neutralizing activity but significant ADE activity toward standard DENV serotypes and imDENV. Hence, it seems responsible to hypothesize that anti-pr4 serum was infection-enhancing antibody and pr4 was infection-enhancing epitope. In conclusion, we characterized a novel infection-enhancing epitope on dengue pr protein, a finding that may provide new insight into the pathogenesis of DENV infection and contribute to dengue vaccine design.
authors.affiliation: Guangzhou Brain Hospital (Guangzhou Huiai hospital, the affiliated hospital of Guangzhou Medical University), Guanghzou, 510370, China, yayanluo@163.com.
authors.forename: Yayan
authors.initials: Y
authors.lastname: Luo
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Guo
authors.forename: Huijun
authors.initials: H
authors.lastname: Yan
authors.forename: Danyun
authors.initials: D
authors.lastname: Fang
authors.forename: Gucheng
authors.initials: G
authors.lastname: Zeng
authors.forename: Junmei
authors.initials: J
authors.lastname: Zhou
authors.forename: Lifang
authors.initials: L
authors.lastname: Jiang
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D019067:Antibody-Dependent Enhancement; D002460:Cell Line; D003716:Dengue Virus / Q000276:immunology* / Q000472:pathogenicity*; D018604:Epitope Mapping; D018985:Epitopes, B-Lymphocyte / Q000276:immunology*; D006801:Humans; D008807:Mice, Inbred BALB C; D014759:Viral Envelope Proteins / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D018985:Epitopes, B-Lymphocyte; D014759:Viral Envelope Proteins; C074932:prM protein, Flavivirus
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