Intranasal delivery of an IgA monoclonal antibody effective against sublethal H5N1 influenza virus infection in mice.
Highly pathogenic avian H5N1 influenza viruses are endemic in poultry in Asia and pose a pandemic threat to humans. Since the deployment of vaccines against a pandemic strain may take several months, adequate antiviral alternatives are needed to minimize the effects and the spread of the disease. Passive immunotherapy is regarded as a viable alternative. Here, we show the development of an IgA monoclonal antibody (DPJY01 MAb) specific to H5 hemagglutinin. The DPJY01 MAb showed a broad hemagglutination inhibition (HI) profile against Asian H5N1 viruses of clades 0, 1.0, 2.1, 2.2, and 2.3 and also against H5 wild bird influenza viruses of the North American and Eurasian lineages. DPJY01 MAb displayed also high neutralization activity in vitro and in vivo. In mice, DPJY01 MAb provided protection via a single dose administered intranasally before or after inoculation with a sublethal dose of H5N1 viruses of clades 1.0 and 2.2. Pretreatment with 50 mg of DPJY01 MAb kg of body weight at either 24, 48, or 72 h before highly pathogenic H5N1 virus (A/Vietnam/1203/2004 [H5N1]) inoculation resulted in complete protection. Treatment with 50 mg/kg at either at 24, 48, or 72 h after H5N1 inoculation provided 100%, 80%, and 60% protection, respectively. These studies highlight the potential use of DPJY01 MAb as an intranasal antiviral treatment for H5N1 influenza virus infections.
Ye
Jianqiang
J
Department of Veterinary Medicine, College Park, MD 20742, USA.
Shao
Hongxia
H
Hickman
Danielle
D
Angel
Matthew
M
Xu
Kemin
K
Cai
Yibin
Y
Song
Haichen
H
Fouchier
Ron A M
RA
Qin
Aijian
A
Perez
Daniel R
DR
D000281:Administration, Intranasal; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000302:isolation & purification; D005260:Female; D006385:Hemagglutination Inhibition Tests; D007070:Immunoglobulin A / Q000008:administration & dosage* / Q000302:isolation & purification; D007167:Immunotherapy / Q000379:methods*; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D009976:Orthomyxoviridae Infections / Q000517:prevention & control* / Q000628:therapy*; D016019:Survival Analysis; D013997:Time Factors
D000911:Antibodies, Monoclonal; D007070:Immunoglobulin A