A broadly neutralizing human monoclonal antibody is effective against H7N9

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 H7N...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2015-09, Vol.112 (35), p.10890-10895
Main Authors: 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., Babcock, Gregory J., Wogan, Gerald N., Sasisekharan, Ram, Shriver, Zachary
Format: Article
Language:English
Subjects:
Animals
Antibodies, Monoclonal - immunology
Antibodies, Monoclonal - therapeutic use
Antibodies, Neutralizing - immunology
Biological Sciences
Cytokines
Health risks
Humans
Influenza
Influenza A Virus, H7N9 Subtype - immunology
Influenza, Human - therapy
Intensive care
Medical treatment
Mice
Mice, Inbred Strains
Monoclonal antibodies
Neutralization
Pandemics
Public health
Respiratory distress syndrome
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1502374112