Comprehensive mapping infection-enhancing epitopes of dengue pr protein using polyclonal antibody against prM

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• 作者：Yayan Luo ; Xiaolan Guo ; Huijun Yan ; Danyun Fang…
• 关键词：Dengue virus ; pr protein ; Epitope ; Synthetic peptides ; Antibody ; dependent enhancement
• 刊名：Applied Microbiology and Biotechnology
• 出版年：2015
• 出版时间：July 2015
• 年：2015
• 卷：99
• 期：14
• 页码：5917-5927
• 全文大小：1,724 KB
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• 作者单位：Yayan Luo (1)
  Xiaolan Guo (2)
  Huijun Yan (2)
  Danyun Fang (2)
  Gucheng Zeng (2)
  Junmei Zhou (2)
  Lifang Jiang (2)
  
  1. Guangzhou Brain Hospital (Guangzhou Huiai hospital, the affiliated hospital of Guangzhou Medical University), Guanghzou, 510370, China
  2. 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
  
• 刊物类别：Chemistry and Materials Science
• 刊物主题：Chemistry
  Biotechnology
  Microbiology
  Microbial Genetics and Genomics
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-0614

文摘

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.