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Cationic Polymers for the Delivery of the Ebola DNA Vaccine Encoding Artificial T-Cell Immunogen

Background: According to current data, an effective Ebola virus vaccine should induce both humoral and T-cell immunity. In this work, we focused our efforts on methods for delivering artificial T-cell immunogen in the form of a DNA vaccine, using generation 4 polyamidoamine dendrimers (PAMAM G4) and...

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Autores principales: Karpenko, Larisa I., Apartsin, Evgeny K., Dudko, Sergei G., Starostina, Ekaterina V., Kaplina, Olga N., Antonets, Denis V., Volosnikova, Ekaterina A., Zaitsev, Boris N., Bakulina, Anastasiya Yu., Venyaminova, Aliya G., Ilyichev, Alexander A., Bazhan, Sergei I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760684/
https://www.ncbi.nlm.nih.gov/pubmed/33271964
http://dx.doi.org/10.3390/vaccines8040718
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author Karpenko, Larisa I.
Apartsin, Evgeny K.
Dudko, Sergei G.
Starostina, Ekaterina V.
Kaplina, Olga N.
Antonets, Denis V.
Volosnikova, Ekaterina A.
Zaitsev, Boris N.
Bakulina, Anastasiya Yu.
Venyaminova, Aliya G.
Ilyichev, Alexander A.
Bazhan, Sergei I.
author_facet Karpenko, Larisa I.
Apartsin, Evgeny K.
Dudko, Sergei G.
Starostina, Ekaterina V.
Kaplina, Olga N.
Antonets, Denis V.
Volosnikova, Ekaterina A.
Zaitsev, Boris N.
Bakulina, Anastasiya Yu.
Venyaminova, Aliya G.
Ilyichev, Alexander A.
Bazhan, Sergei I.
author_sort Karpenko, Larisa I.
collection PubMed
description Background: According to current data, an effective Ebola virus vaccine should induce both humoral and T-cell immunity. In this work, we focused our efforts on methods for delivering artificial T-cell immunogen in the form of a DNA vaccine, using generation 4 polyamidoamine dendrimers (PAMAM G4) and a polyglucin:spermidine conjugate (PG). Methods: Optimal conditions were selected for obtaining complexes of previously developed DNA vaccines with cationic polymers. The sizes, mobility and surface charge of the complexes with PG and PAMAM 4G have been determined. The immunogenicity of the obtained vaccine constructs was investigated in BALB/c mice. Results: It was shown that packaging of DNA vaccine constructs both in the PG envelope and the PAMAM 4G envelope results in an increase in their immunogenicity as compared with the group of mice immunized with the of vector plasmid pcDNA3.1 (a negative control). The highest T-cell responses were shown in mice immunized with complexes of DNA vaccines with PG and these responses significantly exceeded those in the groups of animals immunized with both the combination of naked DNAs and the combination DNAs coated with PAMAM 4G. In the group of animals immunized with complexes of the DNA vaccines with PAMAM 4G, no statistical differences were found in the ability to induce T-cell responses, as compared with the group of mice immunized with the combination of naked DNAs. Conclusions: The PG conjugate can be considered as a promising and safe means to deliver DNA-based vaccines. The use of PAMAM requires further optimization.
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spelling pubmed-77606842020-12-26 Cationic Polymers for the Delivery of the Ebola DNA Vaccine Encoding Artificial T-Cell Immunogen Karpenko, Larisa I. Apartsin, Evgeny K. Dudko, Sergei G. Starostina, Ekaterina V. Kaplina, Olga N. Antonets, Denis V. Volosnikova, Ekaterina A. Zaitsev, Boris N. Bakulina, Anastasiya Yu. Venyaminova, Aliya G. Ilyichev, Alexander A. Bazhan, Sergei I. Vaccines (Basel) Article Background: According to current data, an effective Ebola virus vaccine should induce both humoral and T-cell immunity. In this work, we focused our efforts on methods for delivering artificial T-cell immunogen in the form of a DNA vaccine, using generation 4 polyamidoamine dendrimers (PAMAM G4) and a polyglucin:spermidine conjugate (PG). Methods: Optimal conditions were selected for obtaining complexes of previously developed DNA vaccines with cationic polymers. The sizes, mobility and surface charge of the complexes with PG and PAMAM 4G have been determined. The immunogenicity of the obtained vaccine constructs was investigated in BALB/c mice. Results: It was shown that packaging of DNA vaccine constructs both in the PG envelope and the PAMAM 4G envelope results in an increase in their immunogenicity as compared with the group of mice immunized with the of vector plasmid pcDNA3.1 (a negative control). The highest T-cell responses were shown in mice immunized with complexes of DNA vaccines with PG and these responses significantly exceeded those in the groups of animals immunized with both the combination of naked DNAs and the combination DNAs coated with PAMAM 4G. In the group of animals immunized with complexes of the DNA vaccines with PAMAM 4G, no statistical differences were found in the ability to induce T-cell responses, as compared with the group of mice immunized with the combination of naked DNAs. Conclusions: The PG conjugate can be considered as a promising and safe means to deliver DNA-based vaccines. The use of PAMAM requires further optimization. MDPI 2020-12-01 /pmc/articles/PMC7760684/ /pubmed/33271964 http://dx.doi.org/10.3390/vaccines8040718 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Karpenko, Larisa I.
Apartsin, Evgeny K.
Dudko, Sergei G.
Starostina, Ekaterina V.
Kaplina, Olga N.
Antonets, Denis V.
Volosnikova, Ekaterina A.
Zaitsev, Boris N.
Bakulina, Anastasiya Yu.
Venyaminova, Aliya G.
Ilyichev, Alexander A.
Bazhan, Sergei I.
Cationic Polymers for the Delivery of the Ebola DNA Vaccine Encoding Artificial T-Cell Immunogen
title Cationic Polymers for the Delivery of the Ebola DNA Vaccine Encoding Artificial T-Cell Immunogen
title_full Cationic Polymers for the Delivery of the Ebola DNA Vaccine Encoding Artificial T-Cell Immunogen
title_fullStr Cationic Polymers for the Delivery of the Ebola DNA Vaccine Encoding Artificial T-Cell Immunogen
title_full_unstemmed Cationic Polymers for the Delivery of the Ebola DNA Vaccine Encoding Artificial T-Cell Immunogen
title_short Cationic Polymers for the Delivery of the Ebola DNA Vaccine Encoding Artificial T-Cell Immunogen
title_sort cationic polymers for the delivery of the ebola dna vaccine encoding artificial t-cell immunogen
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760684/
https://www.ncbi.nlm.nih.gov/pubmed/33271964
http://dx.doi.org/10.3390/vaccines8040718
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