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A cross-protective mAb recognizes a novel epitope within the flavivirus NS1 protein.

Abstract
Despite a resurgence of flavivirus infections worldwide, no approved therapeutic agent exists for any member of the genus. While cross-reactive antibodies with therapeutic potential against flaviviruses have been generated, the majority of them are anti-E antibodies with the potential to cause antibody-dependent enhancement of flavivirus infection and disease. We described previously mAbs against the non-structural NS1 protein of the West Nile virus (WNV) that were protective in mice when administered pre- or post-infection of WNV. Here, we demonstrate that one of these mAbs (16NS1) cross-reacted with Japanese encephalitis virus (JEV) and exhibited protective activity against a lethal JEV infection. Overlapping peptide mapping analysis combined with site-specific mutations identified a novel epitope ¹¹⁶KAWGKSILFA¹²⁵ and critical amino acid residues (¹¹⁸W and ¹²²I) for 16NS1 mAb binding. These results may facilitate the development of a broadly therapeutic mAb that lacks enhancing potential and/or subunit-based vaccine against flaviviruses that target the NS1 protein.
AuthorsTae Hee Lee, Byung-Hak Song, Sang-Im Yun, Hye Ryun Woo, Young-Min Lee, Michael S Diamond, Kyung Min Chung
JournalThe Journal of general virology (J Gen Virol) Vol. 93 Issue Pt 1 Pg. 20-26 (Jan 2012) ISSN: 1465-2099 [Electronic] England
PMID21918007 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibodies, Monoclonal
  • Antibodies, Viral
  • Epitopes
  • NS1 protein, Flavivirus
  • Viral Nonstructural Proteins
Topics
  • Animals
  • Antibodies, Monoclonal (immunology)
  • Antibodies, Viral (immunology)
  • Cross Protection
  • Encephalitis Virus, Japanese (genetics, immunology)
  • Encephalitis, Japanese (immunology, virology)
  • Epitope Mapping
  • Epitopes (genetics, immunology)
  • Humans
  • Mice
  • Mice, Inbred ICR
  • Viral Nonstructural Proteins (genetics, immunology)
  • West Nile Fever (immunology, virology)
  • West Nile virus (genetics, immunology)

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