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Publication Abstract from PubMed

There are no approved flaviviral therapies and the development of vaccines against flaviruses has the potential of being undermined by antibody-dependent enhancement (ADE). The flavivirus nonstructural protein 1 (NS1) is a promising vaccine antigen with low ADE risk but has yet to be explored as a broad-spectrum therapeutic antibody target. Here, we provide the structural basis of NS1 antibody cross-reactivity through cocrystallization of the antibody 1G5.3 with NS1 proteins from dengue and Zika viruses. The 1G5.3 antibody blocks multi-flavivirus NS1-mediated cell permeability in disease-relevant cell lines, and therapeutic application of 1G5.3 reduces viremia and improves survival in dengue, Zika, and West Nile virus murine models. Finally, we demonstrate that 1G5.3 protection is independent of effector function, identifying the 1G5.3 epitope as a key site for broad-spectrum antiviral development.

A broadly protective antibody that targets the flavivirus NS1 protein.,Modhiran N, Song H, Liu L, Bletchly C, Brillault L, Amarilla AA, Xu X, Qi J, Chai Y, Cheung STM, Traves R, Setoh YX, Bibby S, Scott CAP, Freney ME, Newton ND, Khromykh AA, Chappell KJ, Muller DA, Stacey KJ, Landsberg MJ, Shi Y, Gao GF, Young PR, Watterson D Science. 2021 Jan 8;371(6525):190-194. doi: 10.1126/science.abb9425. PMID:33414219^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.