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Koloskova O.O.,Moscow State University | Nikonova A.A.,NRC Institute of Immunology | Budanova U.A.,Moscow State University | Shilovskiy I.P.,NRC Institute of Immunology | And 7 more authors.
European Journal of Pharmaceutics and Biopharmaceutics | Year: 2016

Nucleic acid-based therapeutics have recently emerged as a new class of next generation agents for treatment and prevention of viral infection, cancer, and genetic disorders, but their wide use is limited by their relatively weak delivery into target cells. Usage of synthetic cationic amphiphiles with peptide hydrophilic domain as agents for non-viral gene delivery is an attractive approach. We developed the schemes for the synthesis of aliphatic peptides with different length of the hydrocarbon chains in hydrophobic domains and different amino acids in polar head. For the obtained derivatives we determined transfection efficiency, critical vesicle concentration, particle size, ζ-potential and aggregates stability. We have found that the transfection efficiency is increased if the ornithine is a part of polar head in an amphiphile. The most promising amphiphile for liposomal formation OrnOrnGlu(C16H33)2 was examined more carefully. It has been shown that the lipopeptide possesses low toxicity (in vitro and in vivo) and high transfection efficiency with pDNA and siRNA in different cell lines. In addition, the production of liposomes based on this lipopeptide is simple, quick and cheap. Thus OrnOrnGlu(C16H33)2 is a promising vehicle for gene delivery and gene silencing. © 2016 Elsevier B.V. All rights reserved.


PubMed | Moscow State University, RAS Engelhardt Institute of Molecular Biology, NRC Institute of Immunology and Mechnikov Research Institute of Vaccines and Sera
Type: | Journal: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V | Year: 2016

Nucleic acid-based therapeutics have recently emerged as a new class of next generation agents for treatment and prevention of viral infection, cancer, and genetic disorders, but their wide use is limited by their relatively weak delivery into target cells. Usage of synthetic cationic amphiphiles with peptide hydrophilic domain as agents for non-viral gene delivery is an attractive approach. We developed the schemes for the synthesis of aliphatic peptides with different length of the hydrocarbon chains in hydrophobic domains and different amino acids in polar head. For the obtained derivatives we determined transfection efficiency, critical vesicle concentration, particle size, -potential and aggregates stability. We have found that the transfection efficiency is increased if the ornithine is a part of polar head in an amphiphile. The most promising amphiphile for liposomal formation OrnOrnGlu(C16H33)2 was examined more carefully. It has been shown that the lipopeptide possesses low toxicity (in vitro and in vivo) and high transfection efficiency with pDNA and siRNA in different cell lines. In addition, the production of liposomes based on this lipopeptide is simple, quick and cheap. Thus OrnOrnGlu(C16H33)2 is a promising vehicle for gene delivery and gene silencing.


Krylov V.,Mechnikov Research Institute of Vaccines and Sera | Shaburova O.,Mechnikov Research Institute of Vaccines and Sera | Krylov S.,Mechnikov Research Institute of Vaccines and Sera | Pleteneva E.,Mechnikov Research Institute of Vaccines and Sera
Viruses | Year: 2012

Pseudomonas aeruginosa is a frequent participant in wound infections. Emergence of multiple antibiotic resistant strains has created significant problems in the treatment of infected wounds. Phage therapy (PT) has been proposed as a possible alternative approach. Infected wounds are the perfect place for PT applications, since the basic condition for PT is ensured; namely, the direct contact of bacteria and their viruses. Plenty of virulent ("lytic") and temperate ("lysogenic") bacteriophages are known in P. aeruginosa. However, the number of virulent phage species acceptable for PT and their mutability are limited. Besides, there are different deviations in the behavior of virulent (and temperate) phages from their expected canonical models of development. We consider some examples of non-canonical phage-bacterium interactions and the possibility of their use in PT. In addition, some optimal approaches to the development of phage therapy will be discussed from the point of view of a biologist, considering the danger of phage-assisted horizontal gene transfer (HGT), and from the point of view of a surgeon who has accepted the Hippocrates Oath to cure patients by all possible means. It is also time now to discuss the possible approaches in international cooperation for the development of PT. We think it would be advantageous to make phage therapy a kind of personalized medicine. © 2013 by the authors, licensee MDPI, Basel, Switzerland.


Samoylikov P.,Mechnikov Research Institute of Vaccines and Sera | Gervazieva V.,Mechnikov Research Institute of Vaccines and Sera | Kozhevnikov S.,Research Institute of Pediatrics and Pediatric Surgery
World Allergy Organization Journal | Year: 2013

Background: Patients with atopic dermatitis (AD) can develop autoantibodies against intracellular proteins. AD patients often suffer from herpes viruses (HV) infection which complicates the inflammatory process in the skin. The aim of the study was to reveal IgE and IgG antibodies (abs) specific to some skin antigens and to compare their levels with the severity of AD with HV infection in children. Methods: IgE and IgG abs specific to tissue antigens, total IgE, IgE-abs to environmental common allergens as well as IgG abs specific to HV were detected in serum samples by ELISA in 157 AD children. Results: IgE and IgG antibody production to keratin and elastin was observed in children with AD and elevated proportionally to the severity of AD. IgG - abs to herpes simplex virus was increased in children and associated with the severity of clinical course of AD. Conclusion: Our data shown that clinical course of severe AD is accompanied with autoimmune response to epidermal antigens (keratin and elastin). Elevated levels of the autoantibodies, especially against the background of HV infection may be useful serological parameter for monitoring of the disease activity. © 2013 Assarehzadegan et al.; licensee BioMed Central Ltd.


Vasiliev Y.M.,Mechnikov Research Institute of Vaccines and Sera
Expert Review of Vaccines | Year: 2014

A number of preclinical and clinical studies with chitosan-adjuvanted antigen- and DNA-based vaccines have been carried out. Various chitosans and their modifications, in different forms (solutions, powders, gels and particles), have been evaluated with various antigens administered via different routes. Chitosan is a generic name for a wide array of glucosamine-based substances derived from biological sources, and standardization is necessary. However, in most of the studies published to date, molecular weight, viscosity, deacetylation degree and/or purity level (especially endotoxins) are not provided for the initial chitosan substance and/or final formulation and the preparation procedure is not detailed. Evaluation of adjuvant properties is challenging, given that the only available data are insufficient to demonstrate immunogenicity for chitosans with characteristics within certain intervals to elucidate mechanisms of action or to exclude impurities as the active substance. These and other issues of chitosan-based vaccine adjuvants are summarized and a step-by-step evaluation approach for chitosan-based vaccine adjuvants is outlined. © 2015 Informa UK Ltd.


Dmitriev A.D.,Mechnikov Research Institute of Vaccines and Sera | Tarakanova J.N.,Mechnikov Research Institute of Vaccines and Sera | Yakovleva D.A.,Mechnikov Research Institute of Vaccines and Sera | Dmitriev D.A.,Mechnikov Research Institute of Vaccines and Sera | And 8 more authors.
Journal of Immunoassay and Immunochemistry | Year: 2013

This article reexamines some opinions concerning pH requirements for optimal immobilization of monoclonal antibodies (mAbs) by passive adsorption in antigen capture ELISA. It was discovered that substitution of "classical" sodium phosphate (pH 7.5) and carbonate (pH 9.5) coating solutions by acid (pH 2.8) buffers maximized antigen capture 4 out of 10 different tested anti-HBsAg mAbs, resulting in a 1.5-2.5 increase of binding curve coefficients. By measuring both mAbs amounts and functionality, the enhancement effect was attributed to the better preservation of solid phase antibodies activity. Copyright © Taylor & Francis Group, LLC.


Kaloshin A.A.,Mechnikov Research Institute of Vaccines and Sera | Leonova E.I.,Mechnikov Research Institute of Vaccines and Sera | Soldatenkova A.V.,Mechnikov Research Institute of Vaccines and Sera | Mihailova N.A.,Mechnikov Research Institute of Vaccines and Sera
Vestnik Rossiiskoi Akademii Meditsinskikh Nauk | Year: 2016

Pseudomonas aeruginosa induces the complications after burns, injuries, surgical interventions and appears to be one of the main causative agents of nosocomial infections. This pathogen has the high resistance to the antibacterial preparations, therefore the immunoprophylaxis is considered as one of the major approaches to reduce Pseudomonas infection. Objective: The aim of our investigation is to study the protective properties of the recombinant complex of the outer membrane protein F (OprF) and a non-toxic variant of the exotoxin A (toxoid) against Pseudomonas infection. Methods: The recombinant proteins which contained the additional histidine residues were synthesized into Escherichia coli with isopropyl-β- D-thyogalactopyranoside (IPTG). The recombinant proteins were purified by affinity chromatography on Ni-Sepharose. The preparations of recombinant proteins were injected intraperitoneally into the mice. Aluminum hydroxide was used as an adjuvant. For an experimental infection in mice, animals were challenged intraperitoneally by a live virulent culture of P. aeruginosa (PA-103 strain). Results: The best protective effect for the complex containing 25 μg OprF and 50 μg toxoid was identified when we used the double immunization of mice (Index of efficiency of the protective properties in this case was 4.0). Indexes of efficiency of separated recombinant proteins which were injected twice in the same doses were 2.0 for OprF u 2.3 for toxoid. The triple immunization of animals was inefficient for separated recombinant proteins in the same doses. The injection of doses which were lowered twice (12.5 μg for OprF and 25 μg for toxoid) resulted in increased survival of mice immunized by individual proteins (indexes of efficiency: 3 for OprF and u 3,5 for toxoid). However when we administered to the complex of proteins with the same doses Index of efficiency was 2.8. Conclusion: It was shown that the maximum protective effect in a short time is achieved by the combination of double immunization and the mixture of the recombinant proteins OprF and the 25 and 50 μg doses of recombinant toxoid .


Ghendon Y.,Mechnikov Research Institute of Vaccines and Sera | Markushin S.,Mechnikov Research Institute of Vaccines and Sera | Akopova I.,Mechnikov Research Institute of Vaccines and Sera | Koptiaeva I.,Mechnikov Research Institute of Vaccines and Sera | Krivtsov G.,Mechnikov Research Institute of Vaccines and Sera
Journal of Medical Virology | Year: 2011

The use of inactivated poliomyelitis vaccine is very important for eradicating poliomyelitis. However, this vaccine is not available readily in underdeveloped countries due to the high cost. Adjuvants can improve the immunogenicity of a vaccine and reduce the antigen dose required for vaccination, thus lowering the cost of the vaccine. Chitosan glutamate solution and a chitosan sulfate micro/nanoparticle suspension were tested as adjuvants for Imovax-inactivated poliovaccine and for inactivated monovalent poliovirus type 1, 2, and 3 vaccines obtained by inactivation of the attenuated Sabin poliovirus strains. Inactivated vaccines admixed with either chitosan glutamate or chitosan sulfate micro/nanoparticles and administered to mice showed significantly enhanced immunogenicity to poliovirus type 1, 2, and 3 strains compared to the respective vaccines administered without chitosan. Chitosan preparations increased the immunogenicity of 1:2 and 1:4 diluted inactivated Sabin strain preparations in mice 8- to 16-fold, so that the neutralizing antibody titers after vaccination with adjuvanted diluted vaccine were equal to those obtained after vaccination with undiluted vaccine administered without chitosan. Neutralizing antibodies could be detected in sera of rats vaccinated with undiluted, 1:10, and 1:100 diluted Imovax vaccine admixed with chitosan sulfate micro/nanoparticles, although in the control group, vaccination only with the undiluted vaccine resulted in antibody production. These results show that the chitosan glutamate solution and chitosan sulfate micro/nanoparticle suspension can significantly improve the immunogenicity of various poliovaccines, and reduce the effective antigen dose. © 2011 Wiley-Liss, Inc.


PubMed | Mechnikov Research Institute of Vaccines and Sera
Type: Journal Article | Journal: Expert review of vaccines | Year: 2014

A number of preclinical and clinical studies with chitosan-adjuvanted antigen- and DNA-based vaccines have been carried out. Various chitosans and their modifications, in different forms (solutions, powders, gels and particles), have been evaluated with various antigens administered via different routes. Chitosan is a generic name for a wide array of glucosamine-based substances derived from biological sources, and standardization is necessary. However, in most of the studies published to date, molecular weight, viscosity, deacetylation degree and/or purity level (especially endotoxins) are not provided for the initial chitosan substance and/or final formulation and the preparation procedure is not detailed. Evaluation of adjuvant properties is challenging, given that the only available data are insufficient to demonstrate immunogenicity for chitosans with characteristics within certain intervals to elucidate mechanisms of action or to exclude impurities as the active substance. These and other issues of chitosan-based vaccine adjuvants are summarized and a step-by-step evaluation approach for chitosan-based vaccine adjuvants is outlined.


PubMed | Mechnikov Research Institute of Vaccines and Sera
Type: Journal Article | Journal: Journal of medical virology | Year: 2011

The use of inactivated poliomyelitis vaccine is very important for eradicating poliomyelitis. However, this vaccine is not available readily in underdeveloped countries due to the high cost. Adjuvants can improve the immunogenicity of a vaccine and reduce the antigen dose required for vaccination, thus lowering the cost of the vaccine. Chitosan glutamate solution and a chitosan sulfate micro/nanoparticle suspension were tested as adjuvants for Imovax-inactivated poliovaccine and for inactivated monovalent poliovirus type 1, 2, and 3 vaccines obtained by inactivation of the attenuated Sabin poliovirus strains. Inactivated vaccines admixed with either chitosan glutamate or chitosan sulfate micro/nanoparticles and administered to mice showed significantly enhanced immunogenicity to poliovirus type 1, 2, and 3 strains compared to the respective vaccines administered without chitosan. Chitosan preparations increased the immunogenicity of 1:2 and 1:4 diluted inactivated Sabin strain preparations in mice 8- to 16-fold, so that the neutralizing antibody titers after vaccination with adjuvanted diluted vaccine were equal to those obtained after vaccination with undiluted vaccine administered without chitosan. Neutralizing antibodies could be detected in sera of rats vaccinated with undiluted, 1:10, and 1:100 diluted Imovax vaccine admixed with chitosan sulfate micro/nanoparticles, although in the control group, vaccination only with the undiluted vaccine resulted in antibody production. These results show that the chitosan glutamate solution and chitosan sulfate micro/nanoparticle suspension can significantly improve the immunogenicity of various poliovaccines, and reduce the effective antigen dose.

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