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Title: A cross-protective mAb recognizes a novel epitope within the flavivirus NS1 protein. Author: Lee TH, Song BH, Yun SI, Woo HR, Lee YM, Diamond MS, Chung KM. Journal: J Gen Virol; 2012 Jan; 93(Pt 1):20-26. PubMed ID: 21918007. 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.[Abstract] [Full Text] [Related] [New Search]