title: Dose-dependent antiviral activity of released-active form of antibodies to interferon-gamma against influenza A/California/07/09(H1N1) in murine model.
abstract: The assessment of dose-response is an essential part of drug development in terms of the determination of a drug's effective dose, finding the safety endpoint, estimation of the pharmacokinetic profile, and even validation of drug activity, especially for therapeutic agents with a principally novel mechanism of action. Drugs based on released-active forms of antibodies are a good example of such a target. In this study, the efficacy of the antiviral drug Anaferon for children (released-active form of antibodies to interferon-gamma) was tested in a dose-dependent manner (at doses of 0.13, 0.2, 0.4, 0.8 ml/mouse/day) in a murine model of acute pneumonia induced by influenza virus pandemic strain A/California/07/09 (H1N1). Administration of the drug at the two highest doses led to: a reduction in the virus infectious titer in lung tissue up to 4.2 lgEID50/20 mg of tissue; infected animals' life prolongation up to 6.7 days; an increase in the survival rate of up to 40% and a decrease in morphological signs of inflammation when compared to the control animals. In this study, the dose-response effect of Anaferon for Children was demonstrated on mice for the first time. This finding is especially important for drugs with a principally novel mechanism of action like drugs based on released-active forms of antibodies. J. Med. Virol. 89:759-766, 2017. © 2016 Wiley Periodicals, Inc.
authors: The Institute of General Pathology and Pathophysiology, Moscow, Russian Federation.
authors: Еlena S
authors: ЕS
authors: Don
authors: The Institute of General Pathology and Pathophysiology, Moscow, Russian Federation.
authors: Alexandra G
authors: AG
authors: Emelyanova
authors: OOO "NPF "MATERIA MEDICA HOLDING", Moscow, Russian Federation.
authors: Natalia N
authors: NN
authors: Yakovleva
authors: The Institute of General Pathology and Pathophysiology, Moscow, Russian Federation.
authors: Nataliia V
authors: NV
authors: Petrova
authors: OOO "NPF "MATERIA MEDICA HOLDING", Moscow, Russian Federation.
authors: Marina V
authors: MV
authors: Nikiforova
authors: OOO "NPF "MATERIA MEDICA HOLDING", Moscow, Russian Federation.
authors: Evgeniy A
authors: EA
authors: Gorbunov
authors: OOO "NPF "MATERIA MEDICA HOLDING", Moscow, Russian Federation.
authors: Sergey А
authors: SА
authors: Tarasov
authors: The Institute of General Pathology and Pathophysiology, Moscow, Russian Federation.
authors: Sergey G
authors: SG
authors: Morozov
authors: The Institute of General Pathology and Pathophysiology, Moscow, Russian Federation.
authors: Оleg I
authors: ОI
authors: Epstein
mesh_terms: D000818:Animals; D000906:Antibodies / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D007155:Immunologic Factors / Q000008:administration & dosage*; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D008168:Lung / Q000473:pathology / Q000821:virology; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000188:drug therapy*; D011024:Pneumonia, Viral / Q000188:drug therapy*; D016019:Survival Analysis; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000906:Antibodies; D007155:Immunologic Factors; C547732:anaferon
keywords: animal models of infection; antibody-containing preparations; antiviral agents; influenza virus