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

作者：Lee Tae Hee; Song Byung Hak; Yun Sang Im; Woo Hye Ryun; Lee Young Min; Diamond Michael S; Chung Kyung Min^*

来源：Journal of General Virology, 2012, 93: 20-26.

DOI：10.1099/vir.0.036640-0

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 (116)KAWGKSILFA(125) and critical amino acid residues ((118)W and (122)I) 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.

• 出版日期2012-1
• 单位河北医科大学