Antiviral Activity of Anaferon (Pediatric Formulation) in Mice Infected with Pandemic Influenza Virus A(H1N1/09)

Шишкина, Л. Н.; Скарнович, М. О.; Кабанов, А. С.; Сергеев, А. Н.; Olkin, S.E.; Тарасов, С. А.; Belopolskaya, M. V.; Сергеева, С. А.; Epstein, O. I.; Malkova, E. M.; Stavsky, E. A.; Drozdov, I. G.

doi:10.1007/s10517-010-1006-0

Cited by 10 publications

(8 citation statements)

References 2 publications

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“…Antiviral efficacy of AC was repeatedly demonstrated in several experimental animal models as shown by the resolution of symptoms and the reduction of viral titer Susloparov et al, 2004;Shishkina et al, 2010;Tarasov et al, 2012]. In accordance with this study, a defensive effect of oral AC against lethal influenza caused by pandemic influenza virus A/California/07/09 (H1N1)pdm09 in mice was shown in a dose-dependent manner.…”

Section: Discussionsupporting

confidence: 84%

Dose-dependent antiviral activity of released-active form of antibodies to interferon-gamma against influenza A/California/07/09(H1N1) in murine model

Don

Emelyanova

Yakovleva³

et al. 2016

J. Med. Virol.

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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.

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Section: Discussionsupporting

confidence: 84%

Dose-dependent antiviral activity of released-active form of antibodies to interferon-gamma against influenza A/California/07/09(H1N1) in murine model

Don

Emelyanova

Yakovleva³

et al. 2016

J. Med. Virol.

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“…To date, the ability of the hd-anti-IFN-g to regulate functional activity and production of endogenous IFNs, modulate the immune response, and affect the level of natural circulating Abs to IFN-g has already been studied (17,18). Also, the antiviral activity of the hd-anti-IFN-g against influenza and other respiratory infections has been demonstrated in a variety of preclinical and clinical studies (17,(19)(20)(21)(22)(23). Information regarding recent clinical trials can be found on ClinicalTrials.gov (https://clinicaltrials.gov/ct2/results?cond=&term=anaferon&cntry= &state=&city=&dist=).…”

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confidence: 99%

Insights into the Mechanism of Action of Highly Diluted Biologics

Тарасов

Gorbunov

Don

et al. 2020

The Journal of Immunology

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The therapeutic use of Abs in cancer, autoimmunity, transplantation, and other fields is among the major biopharmaceutical advances of the 20th century. Broader use of Ab-based drugs is constrained because of their high production costs and frequent side effects. One promising approach to overcome these limitations is the use of highly diluted Abs, which are produced by gradual reduction of an Ab concentration to an extremely low level. This technology was used to create a group of drugs for the treatment of various diseases, depending on the specificity of the used Abs. Highly diluted Abs to IFN-g (hd-anti-IFN-g) have been demonstrated to be efficacious against influenza and other respiratory infections in a variety of preclinical and clinical studies. In the current study, we provide evidence for a possible mechanism of action of hd-anti-IFN-g. Using high-resolution solution nuclear magnetic resonance spectroscopy, we show that the drug induced conformational changes in the IFN-g molecule. Chemical shift changes occurred in the amino acids located primarily at the dimer interface and at the C-terminal region of IFN-g. These molecular changes could be crucial for the function of the protein, as evidenced by an observed hd-anti-IFN-g-induced increase in the specific binding of IFN-g to its receptor in U937 cells, enhanced induced production of IFN-g in human PBMC culture, and increased survival of influenza A-infected mice.

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“…Dilutions prepared using this technique were found to share a common feature—the ability to directly modify the initial substance, alter its spatial structure and, consequently, its physicochemical and biological properties. RAF-based drug products are referred to as “released-active”, with their efficacy and safety proven by both non-clinical and clinical studies [ 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ]. We also previously demonstrated the possibility of using ELISA tests for examining the effects of both antibody and non-antibody RAFs on the Ag-Abs interaction [ 40 , 41 ].…”

Section: Introductionmentioning

confidence: 99%

Use of Piezoelectric Immunosensors for Detection of Interferon-Gamma Interaction with Specific Antibodies in the Presence of Released-Active Forms of Antibodies to Interferon-Gamma

Don¹,

Farafonova

Pokhil³

et al. 2016

Sensors

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In preliminary ELISA studies where released-active forms (RAF) of antibodies (Abs) to interferon-gamma (IFNg) were added to the antigen-antibody system, a statistically significant difference in absorbance signals obtained in their presence in comparison to placebo was observed. A piezoelectric immunosensor assay was developed to support these data and investigate the effects of RAF Abs to IFNg on the specific interaction between Abs to IFNg and IFNg. The experimental conditions were designed and optimal electrode coating, detection circumstances and suitable chaotropic agents for electrode regeneration were selected. The developed technique was found to provide high repeatability, intermediate precision and specificity. The difference between the analytical signals of RAF Ab samples and those of the placebo was up to 50.8%, whereas the difference between non-specific controls and the placebo was within 5%–6%. Thus, the piezoelectric immunosensor as well as ELISA has the potential to be used for detecting the effects of RAF Abs to IFNg on the antigen-antibody interaction, which might be the result of RAF’s ability to modify the affinity of IFNg to specific/related Abs.

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Antiviral Activity of Anaferon (Pediatric Formulation) in Mice Infected with Pandemic Influenza Virus A(H1N1/09)

Cited by 10 publications

References 2 publications

Dose-dependent antiviral activity of released-active form of antibodies to interferon-gamma against influenza A/California/07/09(H1N1) in murine model

Dose-dependent antiviral activity of released-active form of antibodies to interferon-gamma against influenza A/California/07/09(H1N1) in murine model

Insights into the Mechanism of Action of Highly Diluted Biologics

Use of Piezoelectric Immunosensors for Detection of Interferon-Gamma Interaction with Specific Antibodies in the Presence of Released-Active Forms of Antibodies to Interferon-Gamma

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