Laboratory of Influenza under Pasteur Institute and APcis carried out a study in cooperation with Materia Medica Holding.
The results of non-clinical study of a novel antiviral drug Anaferon for childrenSince 2008, based on our laboratory studies by APcis we have investigated antiviral activity of Anaferon for children (antibodies to interferon-gamma in release-active form manufactured by OOO “NPF “MATERIA MEDICA HOLDING”, Russia), both as monotherapy and in combination with reference antiviral drug (oseltamivir phosphate manufactured by F. Hoffmann–La Roche Ltd., Switzerland) on various experimental in vivo models of influenza virus in mice. Efficacy of the drug against dangerous pandemic influenza virus strain (А/H1N1 (California/07/2009v) and another influenza A virus, A/H3N8 (Equi2/Miami/1/63), highly pathogenic for rodents, was verified. Since seasonal influenza is generally characterized by huge variety of strains, potential broad spectrum antiviral drugs which are deemed highly promising have been investigated.
Experimental in vivo study on mouse model of А/H1N1 virus (California/07/2009v) at infecting dose 10LD50 demonstrated antiviral activity of Anaferon for children (20 mL/kg/day) both as monotherapy and in combination with oseltamivir (10 mg/kg/day). Particularly, Anaferon monotherapy ensured later debut of the infection (+48 hours) after intranasal virus contamination and reduced mortality (-20%). Combined administration of oseltamivir phosphate and Anaferon for children also decreased mortality as compared to the group receiving oseltamivir only.
Health status of mice evaluated by body weight changes evidences that the mice receiving Anaferon for children monotherapy or its combination with oseltamivir phosphate were less sensitive to infection, while convalescence process in surviving animals was faster vs. placebo group. The study on Balb/c mice applying Anaferon for children demonstrated efficacy non inferior to the one of oseltamivir (10 mg/kg/day), however, maximum antiviral effect was obtained from combination of the two drugs (including later debut of the infection and is milder nature in general).
In A/H3N8 (Equi2/Miami/1/63) virus model at infecting dose 5LD50 Anaferon for children (0.4 mL/mouse/day) was applied orally for prevention and therapy and demonstrated higher efficacy as compared to Oseltamivir at 4 mg/kg/day evidenced by statistical reduction in mortality in the course of time. Both drugs, Anaferon and oseltamivir phosphate, reduced duration of clinical manifestations of the infection and increased survivability of animals as compared to placebo.
Therefore, the results of our experiments evidence that efficacy of Anaferon for children is comparable with that of oseltamivir phosphate. Furthermore, Anaferon for children was capable of enhancing antiviral activity of oseltamivir phosphate.
In 2015, we performed further investigation of potential synergistic effect of Anaferon for children and oseltamivir phosphate in cooperation with Laboratory of Influenza under Pasteur Institute.
Anaferon for children monotherapy demonstrated statistically significant reduction in the number of copies of pandemic H1N1 virus strain in contaminated cell culture. Then consecutive testing of combination of Anaferon for children at 3 various doses with oseltamivir at minimum effective dose (20 nM) was carried out against various strains of H1N1 virus (A/Danmark/524/09 Sensitive H1N1p и A/Danmark/528/09 Resistant H1N1p). Anaferon for children reduced viral reproduction in presence of oseltamivir verified by quantitative real-time PCR test assessing the level of virus-specific protein.
As expected, H1N1 virus strain resistant to oseltamivir was completely resistant to neuraminidase inhibitor (oseltamivir, 20 nM). Addition of Anaferon for children to the same dose of oseltamivir reinforced or caused antiviral effect against the strains both sensitive and resistant to oseltamivir including H1N1pdm09 sen (A/Danemark/524/09 sen) and H1N1pdm09 res (A/Danemark/528/09 res), respectively. In combination with oseltamivir, 20 nM, Anaferon for children showed tendency for delaying replication of the virus by 24 hours approximately.
The study results evidence that Anaferon for children efficacy may be achieved by delay or inhibition of virus synthesis or stimulation of production of endogenous cytokines by cells and activation of intracellular antiviral mechanisms. However, after single administration even prior to contamination inhibition is mild and incomplete. Antiviral activity of Anaferon for children is similar for various strains of influenza virus causing epidemics of this disease and is observed in presence of oseltamivir, 20 nM, and therefore should supplement conventional therapeutic doses of reference antiviral drug. Efficacy of Anaferon for children supplements the effect of oseltamivir, and subsequent increase in antiviral activity seems to be independent of neuraminidase inhibition verified by fluorescent MUNANA method.
Therefore, Anaferon for children demonstrated certain antiviral activity on several in vitro and in vivo influenza A models including pandemic A/H1N1 influenza, both as monotherapy and in combination with oseltamivir. This drug may be recommended as an effective therapy and prevention of influenza A viruses in the countries where its efficacy and safety for humans have been documented.
Source: http://www.ap6.fr/2016/01/27/news-from-the-cold-pasteur-institute-flu-laboratory-and-apcis-make-collaborative-research-with-materia-medica-holding Pasteur Institute Flu laboratory and APcis make collaborative research with Materia Medica Holding