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4G2 (also known as D1-4G2) is a widely utilized mouse monoclonal antibody (IgG2a) that recognizes a highly conserved epitope within the fusion loop of the flavivirus envelope (E) protein. It exhibits broad cross-reactivity across the *Flavivirus* genus, including all four serotypes of Dengue virus (DENV-1, DENV-2, DENV-3, DENV-4), Zika virus (ZIKV), West Nile virus (WNV), and Yellow Fever virus (YFV). Primarily employed as a diagnostic and research reagent in assays such as ELISA, immunofluorescence, and neutralization tests, 4G2 has also been investigated for its potential in passive immunotherapy. A significant characteristic of 4G2 is its role in antibody-dependent enhancement (ADE), where sub-neutralizing levels of the antibody can facilitate viral entry into Fc-receptor-expressing cells, potentially exacerbating disease severity. Consequently, therapeutic development often involves engineering the Fc region of 4G2-derived antibodies to eliminate Fc-gamma receptor binding while maintaining neutralization potency.
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