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

      The Journal of General Virology

      immunology, Animals, genetics, West Nile virus, virology, West Nile Fever, Viral Nonstructural Proteins, Mice, Inbred ICR, Mice, Humans, Epitopes, Epitope Mapping, Encephalitis, Japanese, Encephalitis Virus, Japanese, Cross Protection, Antibodies, Viral, Antibodies, Monoclonal

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          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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          Journal
          10.1099/vir.0.036640-0
          21918007

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