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Article: Dendrimer-Mediated Delivery of DNA and RNA Vaccines.

Kisakova, Lyubov A / Apartsin, Evgeny K / Nizolenko, Lily F / Karpenko, Larisa I

2023 Volume 15, Issue 4

Abstract: DNA and RNA vaccines (nucleic acid-based vaccines) are a promising platform for vaccine development. The first mRNA vaccines (Moderna and Pfizer/BioNTech) were approved in 2020, and a DNA vaccine (Zydus Cadila, India), in 2021. They display unique ... ...

Abstract	DNA and RNA vaccines (nucleic acid-based vaccines) are a promising platform for vaccine development. The first mRNA vaccines (Moderna and Pfizer/BioNTech) were approved in 2020, and a DNA vaccine (Zydus Cadila, India), in 2021. They display unique benefits in the current COVID-19 pandemic. Nucleic acid-based vaccines have a number of advantages, such as safety, efficacy, and low cost. They are potentially faster to develop, cheaper to produce, and easier to store and transport. A crucial step in the technology of DNA or RNA vaccines is choosing an efficient delivery method. Nucleic acid delivery using liposomes is the most popular approach today, but this method has certain disadvantages. Therefore, studies are actively underway to develop various alternative delivery methods, among which synthetic cationic polymers such as dendrimers are very attractive. Dendrimers are three-dimensional nanostructures with a high degree of molecular homogeneity, adjustable size, multivalence, high surface functionality, and high aqueous solubility. The biosafety of some dendrimers has been evaluated in several clinical trials presented in this review. Due to these important and attractive properties, dendrimers are already being used to deliver a number of drugs and are being explored as promising carriers for nucleic acid-based vaccines. This review summarizes the literature data on the development of dendrimer-based delivery systems for DNA and mRNA vaccines.
Language	English
Publishing date	2023-03-30
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics15041106
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Article ; Online: The use of electroporation to deliver DNA-based vaccines

Denis N Kisakov / Igor M. Belyakov / Lubov A Kisakova / Vladimir A Yakovlev / Elena V Tigeeva / Larisa I Karpenko

Expert Review of Vaccines, Vol 23, Iss 1, Pp 102-

2024 Volume 123

Abstract: ABSTRACTIntroduction Nucleic acids represent a promising platform for creating vaccines. One disadvantage of this approach is its relatively low immunogenicity. Electroporation (EP) is an effective way to increase the DNA vaccines immunogenicity. However, ...

Abstract	ABSTRACTIntroduction Nucleic acids represent a promising platform for creating vaccines. One disadvantage of this approach is its relatively low immunogenicity. Electroporation (EP) is an effective way to increase the DNA vaccines immunogenicity. However, due to the different configurations of devices used for EP, EP protocols optimization is required not only to enhance immunogenicity, but also to ensure greater safety and tolerability of the EP procedure.Area covered An data analysis for recent years on the DNA vaccines delivery against viral and parasitic infections using EP was carried out. The study of various EP physical characteristics, such as frequency, pulse duration, pulse interval, should be considered along with the immunogenic construct design and the site of delivery of the vaccine, through the study of the immunogenic and protective characteristics of the latter.Expert opinion Future research should focus on regulating the humoral and cellular response required for protection against infectious agents by modifying the EP protocol. Significant efforts will be directed to establishing the possibility of redirecting the immune response toward the Th1 or Th2 response by changing the EP physical parameters. It will allow for an individual selective approach during EP, depending on the pathogen type of an infectious disease.
Keywords	Vaccines ; DNA ; electroporation ; virus ; bacteria ; protection ; Internal medicine ; RC31-1245
Language	English
Publishing date	2024-12-01T00:00:00Z
Publisher	Taylor & Francis Group
Document type	Article ; Online
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Article ; Online: The use of electroporation to deliver DNA-based vaccines.

Kisakov, Denis N / Belyakov, Igor M / Kisakova, Lubov A / Yakovlev, Vladimir A / Tigeeva, Elena V / Karpenko, Larisa I

Expert review of vaccines

2023 Volume 23, Issue 1, Page(s) 102–123

Abstract: Introduction: Nucleic acids represent a promising platform for creating vaccines. One disadvantage of this approach is its relatively low immunogenicity. Electroporation (EP) is an effective way to increase the DNA vaccines immunogenicity. However, due ... ...

Abstract	Introduction: Nucleic acids represent a promising platform for creating vaccines. One disadvantage of this approach is its relatively low immunogenicity. Electroporation (EP) is an effective way to increase the DNA vaccines immunogenicity. However, due to the different configurations of devices used for EP, EP protocols optimization is required not only to enhance immunogenicity, but also to ensure greater safety and tolerability of the EP procedure. Area covered: An data analysis for recent years on the DNA vaccines delivery against viral and parasitic infections using EP was carried out. The study of various EP physical characteristics, such as frequency, pulse duration, pulse interval, should be considered along with the immunogenic construct design and the site of delivery of the vaccine, through the study of the immunogenic and protective characteristics of the latter. Expert opinion: Future research should focus on regulating the humoral and cellular response required for protection against infectious agents by modifying the EP protocol. Significant efforts will be directed to establishing the possibility of redirecting the immune response toward the Th1 or Th2 response by changing the EP physical parameters. It will allow for an individual selective approach during EP, depending on the pathogen type of an infectious disease.
MeSH term(s)	Humans ; Vaccines, DNA ; Electroporation/methods ; DNA
Chemical Substances	Vaccines, DNA ; DNA (9007-49-2)
Language	English
Publishing date	2023-12-18
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2181284-6
ISSN	1744-8395 ; 1476-0584
ISSN (online)	1744-8395
ISSN	1476-0584
DOI	10.1080/14760584.2023.2292772
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Article: Immunogenic and Protective Properties of Recombinant Hemagglutinin of Influenza A (H5N8) Virus.

Rudometova, Nadezhda B / Fando, Anastasia A / Kisakova, Lyubov A / Kisakov, Denis N / Borgoyakova, Mariya B / Litvinova, Victoria R / Yakovlev, Vladimir A / Tigeeva, Elena V / Vahitov, Danil I / Sharabrin, Sergey V / Shcherbakov, Dmitriy N / Evseenko, Veronika I / Ivanova, Ksenia I / Gudymo, Andrei S / Ilyicheva, Tatiana N / Marchenko, Vasiliy Yu / Ilyichev, Alexander A / Rudometov, Andrey P / Karpenko, Larisa I

Vaccines

2024 Volume 12, Issue 2

Abstract: In this study, we characterized recombinant hemagglutinin (HA) of influenza A (H5N8) virus produced in Chinese hamster ovary cells (CHO-K1s). Immunochemical analysis showed that the recombinant hemagglutinin was recognized by the serum of ferrets ... ...

Abstract	In this study, we characterized recombinant hemagglutinin (HA) of influenza A (H5N8) virus produced in Chinese hamster ovary cells (CHO-K1s). Immunochemical analysis showed that the recombinant hemagglutinin was recognized by the serum of ferrets infected with influenza A (H5N8) virus, indicating that its antigenic properties were retained. Two groups of Balb/c mice were immunized with intramuscular injection of recombinant hemagglutinin or propiolactone inactivated A/Astrakhan/3212/2020 (H5N8) influenza virus. The results demonstrated that both immunogens induced a specific antibody response as determined by ELISA. Virus neutralization assay revealed that sera of immunized animals were able to neutralize A/turkey/Stavropol/320-01/2020 (H5N8) influenza virus-the average neutralizing titer was 2560. Immunization with both recombinant HA/H5 hemagglutinin and inactivated virus gave 100% protection against lethal H5N8 virus challenge. This study shows that recombinant HA (H5N8) protein may be a useful antigen candidate for developing subunit vaccines against influenza A (H5N8) virus with suitable immunogenicity and protective efficacy.
Language	English
Publishing date	2024-01-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2703319-3
ISSN	2076-393X
ISSN	2076-393X
DOI	10.3390/vaccines12020143
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Article ; Online: Genetic Diversity and Drug Resistance Mutations in Reverse Transcriptase and Protease Genes of HIV-1 Isolates from Southwestern Siberia.

Rudometova, Nadezhda B / Shcherbakova, Nadezhda S / Shcherbakov, Dmitry N / Mishenova, Elena V / Delgado, Elena / Ilyichev, Alexander A / Karpenko, Larisa I / Thomson, Michael M

AIDS research and human retroviruses

2021 Volume 37, Issue 9, Page(s) 716–723

Abstract: The analysis of ... ...

Abstract	The analysis of a
MeSH term(s)	Drug Resistance ; Drug Resistance, Viral/genetics ; Genotype ; HIV Infections/epidemiology ; HIV Protease/genetics ; HIV Reverse Transcriptase/genetics ; HIV-1/genetics ; Humans ; Mutation ; Peptide Hydrolases ; Phylogeny ; RNA-Directed DNA Polymerase ; Siberia/epidemiology
Chemical Substances	HIV Reverse Transcriptase (EC 2.7.7.49) ; RNA-Directed DNA Polymerase (EC 2.7.7.49) ; Peptide Hydrolases (EC 3.4.-) ; HIV Protease (EC 3.4.23.-)
Language	English
Publishing date	2021-04-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639130-8
ISSN	1931-8405 ; 0889-2229
ISSN (online)	1931-8405
ISSN	0889-2229
DOI	10.1089/AID.2020.0225
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Zs.A 1928: Show issues

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Jg. 1995 - 2021: Lesesall (1.OG)
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Article ; Online: Enhancing the Immunogenicity of Vaccinia Virus.

Shchelkunov, Sergei N / Yakubitskiy, Stanislav N / Sergeev, Alexander A / Starostina, Ekaterina V / Titova, Ksenia A / Pyankov, Stepan A / Shchelkunova, Galina A / Borgoyakova, Mariya B / Zadorozhny, Alexey M / Orlova, Lyubov A / Kisakov, Denis N / Karpenko, Larisa I

Viruses

2022 Volume 14, Issue 7

Abstract: The conventional live smallpox vaccine based on the vaccinia virus (VACV) cannot be widely used today because it is highly reactogenic. Therefore, there is a demand for designing VACV variants possessing enhanced immunogenicity, making it possible to ... ...

Abstract	The conventional live smallpox vaccine based on the vaccinia virus (VACV) cannot be widely used today because it is highly reactogenic. Therefore, there is a demand for designing VACV variants possessing enhanced immunogenicity, making it possible to reduce the vaccine dose and, therefore, significantly eliminate the pathogenic effect of the VACV on the body. In this study, we analyzed the development of the humoral and T cell-mediated immune responses elicited by immunizing mice with low-dose VACV variants carrying the mutant
MeSH term(s)	Animals ; Mice ; Mice, Inbred BALB C ; Smallpox/prevention & control ; Smallpox Vaccine/genetics ; Vaccines, Attenuated/genetics ; Vaccinia ; Vaccinia virus
Chemical Substances	Smallpox Vaccine ; Vaccines, Attenuated
Language	English
Publishing date	2022-06-30
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v14071453
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Article: SARS-CoV-2 RBD Conjugated to Polyglucin, Spermidine, and dsRNA Elicits a Strong Immune Response in Mice.

Volosnikova, Ekaterina A / Merkuleva, Iuliia A / Esina, Tatiana I / Shcherbakov, Dmitry N / Borgoyakova, Mariya B / Isaeva, Anastasiya A / Nesmeyanova, Valentina S / Volkova, Natalia V / Belenkaya, Svetlana V / Zaykovskaya, Anna V / Pyankov, Oleg V / Starostina, Ekaterina V / Zadorozhny, Alexey M / Zaitsev, Boris N / Karpenko, Larisa I / Ilyichev, Alexander A / Danilenko, Elena D

Vaccines

2023 Volume 11, Issue 4

Abstract: Despite the rapid development and approval of several COVID vaccines based on the full-length spike protein, there is a need for safe, potent, and high-volume vaccines. Considering the predominance of the production of neutralizing antibodies targeting ... ...

Abstract	Despite the rapid development and approval of several COVID vaccines based on the full-length spike protein, there is a need for safe, potent, and high-volume vaccines. Considering the predominance of the production of neutralizing antibodies targeting the receptor-binding domain (RBD) of S-protein after natural infection or vaccination, it makes sense to choose RBD as a vaccine immunogen. However, due to its small size, RBD exhibits relatively poor immunogenicity. Searching for novel adjuvants for RBD-based vaccine formulations is considered a good strategy for enhancing its immunogenicity. Herein, we assess the immunogenicity of severe acute respiratory syndrome coronavirus 2 RBD conjugated to a polyglucin:spermidine complex (PGS) and dsRNA (RBD-PGS + dsRNA) in a mouse model. BALB/c mice were immunized intramuscularly twice, with a 2-week interval, with 50 µg of RBD, RBD with Al(OH)
Language	English
Publishing date	2023-04-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2703319-3
ISSN	2076-393X
ISSN	2076-393X
DOI	10.3390/vaccines11040808
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Article ; Online: Synthesis and In Vitro Study of Antiviral Activity of Glycyrrhizin Nicotinate Derivatives against HIV-1 Pseudoviruses and SARS-CoV-2 Viruses.

Fomenko, Vladislav V / Rudometova, Nadezhda B / Yarovaya, Olga I / Rogachev, Artem D / Fando, Anastasia A / Zaykovskaya, Anna V / Komarova, Nina I / Shcherbakov, Dmitry N / Pyankov, Oleg V / Pokrovsky, Andrey G / Karpenko, Larisa I / Maksyutov, Rinat A / Salakhutdinov, Nariman F

Molecules (Basel, Switzerland)

2022 Volume 27, Issue 1

Abstract: When developing drugs against SARS-CoV-2, it is important to consider the characteristics of patients with different co-morbidities. People infected with HIV-1 are a particularly vulnerable group, as they may be at a higher risk than the general ... ...

Abstract	When developing drugs against SARS-CoV-2, it is important to consider the characteristics of patients with different co-morbidities. People infected with HIV-1 are a particularly vulnerable group, as they may be at a higher risk than the general population of contracting COVID-19 with clinical complications. For such patients, drugs with a broad spectrum of antiviral activity are of paramount importance. Glycyrrhizinic acid (Glyc) and its derivatives are promising biologically active compounds for the development of such broad-spectrum antiviral agents. In this work, derivatives of Glyc obtained by acylation with nicotinic acid were investigated. The resulting preparation, Glycyvir, is a multi-component mixture containing mainly mono-, di-, tri- and tetranicotinates. The composition of Glycyvir was characterized by HPLC-MS/MS and its toxicity assessed in cell culture. Antiviral activity against three strains of SARS-CoV-2 was tested in vitro on Vero E6 cells by MTT assay. Glycyvir was shown to inhibit SARS-CoV-2 replication in vitro (IC
MeSH term(s)	Animals ; Antiviral Agents/chemical synthesis ; Antiviral Agents/pharmacology ; COVID-19/virology ; Chlorocebus aethiops ; Glycyrrhizic Acid/chemistry ; HIV Infections/drug therapy ; HIV Infections/virology ; HIV-1/drug effects ; HeLa Cells ; Humans ; In Vitro Techniques ; SARS-CoV-2/drug effects ; Vero Cells ; Virus Replication ; COVID-19 Drug Treatment
Chemical Substances	Antiviral Agents ; Glycyrrhizic Acid (6FO62043WK)
Language	English
Publishing date	2022-01-04
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules27010295
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Article ; Online: Adaptive Immune Response to Vaccinia Virus LIVP Infection of BALB/c Mice and Protection against Lethal Reinfection with Cowpox Virus.

Shchelkunov, Sergei N / Sergeev, Alexander A / Yakubitskiy, Stanislav N / Titova, Ksenia A / Pyankov, Stepan A / Kolosova, Irina V / Starostina, Ekaterina V / Borgoyakova, Mariya B / Zadorozhny, Alexey M / Kisakov, Denis N / Shulgina, Irina S / Karpenko, Larisa I

Viruses

2021 Volume 13, Issue 8

Abstract: Mass vaccination has played a critical role in the global eradication of smallpox. Various vaccinia virus (VACV) strains, whose origin has not been clearly documented in most cases, have been used as live vaccines in different countries. These VACV ... ...

Abstract	Mass vaccination has played a critical role in the global eradication of smallpox. Various vaccinia virus (VACV) strains, whose origin has not been clearly documented in most cases, have been used as live vaccines in different countries. These VACV strains differed in pathogenicity towards various laboratory animals and in reactogenicity exhibited upon vaccination of humans. In this work, we studied the development of humoral and cellular immune responses in BALB/c mice inoculated intranasally (i.n.) or intradermally (i.d.) with the VACV LIVP strain at a dose of 10
MeSH term(s)	Adaptive Immunity ; Animals ; Antibodies, Viral/immunology ; Cowpox/immunology ; Cowpox/prevention & control ; Cowpox/virology ; Cowpox virus/genetics ; Cowpox virus/immunology ; Cowpox virus/physiology ; Humans ; Mice ; Mice, Inbred BALB C ; Reinfection/immunology ; Reinfection/prevention & control ; Reinfection/virology ; T-Lymphocytes/immunology ; Vaccines, Attenuated/administration & dosage ; Vaccines, Attenuated/immunology ; Vaccinia/immunology ; Vaccinia/virology ; Vaccinia virus/genetics ; Vaccinia virus/immunology ; Vaccinia virus/physiology ; Viral Vaccines/administration & dosage ; Viral Vaccines/immunology
Chemical Substances	Antibodies, Viral ; Vaccines, Attenuated ; Viral Vaccines
Language	English
Publishing date	2021-08-17
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v13081631
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Article ; Online: Synthesis and In Vitro Study of Antiviral Activity of Glycyrrhizin Nicotinate Derivatives against HIV-1 Pseudoviruses and SARS-CoV-2 Viruses

Vladislav V. Fomenko / Nadezhda B. Rudometova / Olga I. Yarovaya / Artem D. Rogachev / Anastasia A. Fando / Anna V. Zaykovskaya / Nina I. Komarova / Dmitry N. Shcherbakov / Oleg V. Pyankov / Andrey G. Pokrovsky / Larisa I. Karpenko / Rinat A. Maksyutov / Nariman F. Salakhutdinov

Molecules, Vol 27, Iss 295, p

2022 Volume 295

Abstract	When developing drugs against SARS-CoV-2, it is important to consider the characteristics of patients with different co-morbidities. People infected with HIV-1 are a particularly vulnerable group, as they may be at a higher risk than the general population of contracting COVID-19 with clinical complications. For such patients, drugs with a broad spectrum of antiviral activity are of paramount importance. Glycyrrhizinic acid (Glyc) and its derivatives are promising biologically active compounds for the development of such broad-spectrum antiviral agents. In this work, derivatives of Glyc obtained by acylation with nicotinic acid were investigated. The resulting preparation, Glycyvir, is a multi-component mixture containing mainly mono-, di-, tri- and tetranicotinates. The composition of Glycyvir was characterized by HPLC-MS/MS and its toxicity assessed in cell culture. Antiviral activity against three strains of SARS-CoV-2 was tested in vitro on Vero E6 cells by MTT assay. Glycyvir was shown to inhibit SARS-CoV-2 replication in vitro (IC 50 2–8 μM) with an antiviral activity comparable to the control drug Remdesivir. In addition, Glycyvir exhibited marked inhibitory activity against HIV pseudoviruses of subtypes B, A6 and the recombinant form CRF63_02A (IC 50 range 3.9–27.5 µM). The time-dependence of Glycyvir inhibitory activity on HIV pseudovirus infection of TZM-bl cells suggested that the compound interfered with virus entry into the target cell. Glycyvir is a promising candidate as an agent with low toxicity and a broad spectrum of antiviral action.
Keywords	human immunodeficiency virus type 1 ; SARS-CoV-2 ; entry inhibitors ; nicotinates of glycyrrhizic acid ; Organic chemistry ; QD241-441
Subject code	570
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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