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 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.
Department of Biological Engineering, Koch Institute of Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;
Kannan
K
Tharakaraman
Department of Biological Engineering, Koch Institute of Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;
Vidya
V
Subramanian
Visterra, Inc., Cambridge, MA 02139;
Karthik
K
Viswanathan
Visterra, Inc., Cambridge, MA 02139;
Susan
S
Sloan
School of Public Health, The University of Hong Kong, Hong Kong Special Administrative Region of China, Pokfulam, Hong Kong;
Hui-Ling
HL
Yen
Institute of Antiviral Research, Utah State University, Logan, UT 84322.
Dale L
DL
Barnard
School of Public Health, The University of Hong Kong, Hong Kong Special Administrative Region of China, Pokfulam, Hong Kong;
Y H Connie
YH
Leung
Visterra, Inc., Cambridge, MA 02139;
Kristy J
KJ
Szretter
Visterra, Inc., Cambridge, MA 02139;
Tyree J
TJ
Koch
Visterra, Inc., Cambridge, MA 02139;
James C
JC
Delaney
Visterra, Inc., Cambridge, MA 02139;
Gregory J
GJ
Babcock
Department of Biological Engineering, Koch Institute of Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139; wogan@mit.edu rams@mit.edu zshriver@visterrainc.com.
Gerald N
GN
Wogan
Department of Biological Engineering, Koch Institute of Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139; wogan@mit.edu rams@mit.edu zshriver@visterrainc.com.
Ram
R
Sasisekharan
Visterra, Inc., Cambridge, MA 02139; wogan@mit.edu rams@mit.edu zshriver@visterrainc.com.
Zachary
Z
Shriver
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000080908:Broadly Neutralizing Antibodies; D006801:Humans; D064766:Influenza A Virus, H7N9 Subtype / Q000276:immunology*; D007251:Influenza, Human / Q000628:therapy; D051379:Mice; D008815:Mice, Inbred Strains
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D057134:Antibodies, Neutralizing; D000080908:Broadly Neutralizing Antibodies; C000613160:VIS410 monoclonal antibody
H7N9; antibody; influenza; virus