A broadly neutralizing human monoclonal antibody is effective against H7N9
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Tharakaraman-2015-Broadly neutralizing.pdf
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Author(s) • • • • • • • • •
Tharakaraman, Kannan
Subramanian, Vidya
Viswanathan, Karthik
Sloan, Susan
Yen, Hui-Ling
Barnard, Dale L.
Leung, Y. H. Connie
Szretter, Kristy J.
Koch, Tyree J.
Delaney, James C.
Date Issued
September 2015
Journal
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences (U.S.)
Citation
Tharakaraman, Kannan, Vidya Subramanian, Karthik Viswanathan, Susan Sloan, Hui-Ling Yen, Dale L. Barnard, Y. H. Connie Leung, et al. “A Broadly Neutralizing Human Monoclonal Antibody Is Effective Against H7N9.” Proc Natl Acad Sci USA 112, no. 35 (August 17, 2015): 10890–10895.
Version
Final published version
Abstract
Emerging strains of influenza represent a significant public health threat with potential pandemic consequences. Of particular concern are the recently emerged H7N9 strains which cause pneumonia with acute respiratory distress syndrome. Estimates are that nearly 80% of hospitalized patients with H7N9 have received intensive care unit support. VIS410, a human antibody, targets a unique conserved epitope on influenza A. We evaluated the efficacy of VIS410 for neutralization of group 2 influenza strains, including H3N2 and H7N9 strains in vitro and in vivo. VIS410, administered at 50 mg/kg, protected DBA mice infected with A/Anhui/2013 (H7N9), resulting in significant survival benefit upon single-dose (−24 h) or double-dose (−12 h, +48 h) administration (P < 0.001). A single dose of VIS410 at 50 mg/kg (−12 h) combined with oseltamivir at 50 mg/kg (−12 h, twice daily for 7 d) in C57BL/6 mice infected with A/Shanghai 2/2013 (H7N9) resulted in significant decreased lung viral load (P = 0.002) and decreased lung cytokine responses for nine of the 11 cytokines measured. Based on these results, we find that VIS410 may be effective either as monotherapy or combined with antivirals in treating H7N9 disease, as well as disease from other influenza strains.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. School of Engineering
Koch Institute for Integrative Cancer Research at MIT
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DOI of Published Version
https://doi.org/10.1073/pnas.1502374112