title: Substitution of the precursor peptide prevents anti-prM antibody-mediated antibody-dependent enhancement of dengue virus infection.
abstract: Antibody-dependent enhancement (ADE) is currently considered as the mechanism underlying the pathogenesis of severe dengue disease. Many studies have shown that precursor (pr) peptide-specific antibodies do not efficiently neutralize infection but potently promote ADE of dengue virus (DENV) infection. To explore the effect of pr peptide substitution on neutralization and ADE of DENV infection, the rabbit anti-prM polyclonal antibodies (pAbs) and anti-JEVpr/DENV-M pAbs were prepared, and the neutralization and ADE of these two pAbs were further compared. Here, we report that both anti-JEVpr/DENV-M and anti-prM pAbs exhibited broad cross-reactivity and only partial neutralization with four DENV serotypes and immature DENV. Rabbit anti-prM pAbs showed a significant enhancement in a broad range of serum dilutions. However, there was no statistically significant difference in the enhancing activity of rabbit anti-JEVpr/DENV-M pAbs at various levels of dilution. These results demonstrate that anti-prM antibody-mediated ADE can be prevented by JEV pr peptide replacement. The present study contribute further to research on 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, Guangdong, 510080, PR China; Institute of Nanomedicine Technology, Department of Laboratory Medicine, Institutional Key Laboratory of Clinical Laboratory Diagnostics, 12th 5-Year Project of Shandong Province, Weifang Medical University, Weifang, Shandong, 261053, PR China. Electronic address: ying0915ai@163.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
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, Guangdong, 510080, PR China. Electronic address: silulu2006324@163.com.
authors.forename: Lu-Lu
authors.initials: LL
authors.lastname: Si
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, Guangdong, 510080, PR China. Electronic address: xiaolan_g@126.com.
authors.forename: Xiao-Lan
authors.initials: XL
authors.lastname: Guo
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, Guangdong, 510080, PR China. Electronic address: 1375710136@qq.com.
authors.forename: Guo-Hui
authors.initials: GH
authors.lastname: Cui
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, Guangdong, 510080, PR China. Electronic address: fangdy@mail.sysu.edu.cn.
authors.forename: Dan-Yun
authors.initials: DY
authors.lastname: Fang
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, Guangdong, 510080, PR China. Electronic address: zhoujunm@mail.sysu.edu.cn.
authors.forename: Jun-Mei
authors.initials: JM
authors.lastname: Zhou
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, Guangdong, 510080, PR China. Electronic address: yanhj@mail.sysu.edu.cn.
authors.forename: Hui-Jun
authors.initials: HJ
authors.lastname: Yan
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, Guangdong, 510080, PR China. Electronic address: jianglf@mail.sysu.edu.cn.
authors.forename: Li-Fang
authors.initials: LF
authors.lastname: Jiang
mesh_terms: D000330:Aedes / Q000166:cytology / Q000821:virology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000737:chemistry*; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000737:chemistry*; D019067:Antibody-Dependent Enhancement; D002460:Cell Line; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D003429:Cross Reactions; D003716:Dengue Virus / Q000235:genetics / Q000254:growth & development / Q000276:immunology*; D004664:Encephalitis Virus, Japanese / Q000235:genetics / Q000276:immunology; D004847:Epithelial Cells / Q000276:immunology / Q000821:virology; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D005822:Genetic Vectors / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D010455:Peptides / Q000235:genetics / Q000276:immunology; D011498:Protein Precursors / Q000235:genetics / Q000276:immunology*; D011817:Rabbits; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D019595:Severe Dengue / Q000276:immunology / Q000821:virology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D010455:Peptides; D011498:Protein Precursors; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins
keywords: Anti-prM antibody; Antibody-dependent enhancement; Chimeric protein; Dengue virus; Pre-membrane; Precursor peptide