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.
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Authors | Tae Hee Lee, Byung-Hak Song, Sang-Im Yun, Hye Ryun Woo, Young-Min Lee, Michael S Diamond, Kyung Min Chung |
Journal | The Journal of general virology
(J Gen Virol)
Vol. 93
Issue Pt 1
Pg. 20-26
(Jan 2012)
ISSN: 1465-2099 [Electronic] England |
PMID | 21918007
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies, Monoclonal
- Antibodies, Viral
- Epitopes
- NS1 protein, Flavivirus
- Viral Nonstructural Proteins
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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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