{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T15:34:39Z","timestamp":1784043279088,"version":"3.55.0"},"reference-count":49,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The study was funded by state assignment","award":["GZ-25\/16"],"award-info":[{"award-number":["GZ-25\/16"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/vaccines8040718","type":"journal-article","created":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T20:06:09Z","timestamp":1606853169000},"page":"718","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Cationic Polymers for the Delivery of the Ebola DNA Vaccine Encoding Artificial T-Cell Immunogen"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4365-8809","authenticated-orcid":false,"given":"Larisa I.","family":"Karpenko","sequence":"first","affiliation":[{"name":"State Research Center of Virology and Biotechnology \u201cVector\u201d, Koltsovo, 630559 Novosibirsk Region, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3334-0397","authenticated-orcid":false,"given":"Evgeny K.","family":"Apartsin","sequence":"additional","affiliation":[{"name":"Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences, 630090 Novosibirsk, Russia"},{"name":"Department of Natural Sciences, Novosibirsk State University, 630090 Novosibirsk, Russia"},{"name":"Laboratoire de Chimie de Coordination, CNRS, 31077 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergei G.","family":"Dudko","sequence":"additional","affiliation":[{"name":"State Research Center of Virology and Biotechnology \u201cVector\u201d, Koltsovo, 630559 Novosibirsk Region, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina V.","family":"Starostina","sequence":"additional","affiliation":[{"name":"State Research Center of Virology and Biotechnology \u201cVector\u201d, Koltsovo, 630559 Novosibirsk Region, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga N.","family":"Kaplina","sequence":"additional","affiliation":[{"name":"State Research Center of Virology and Biotechnology \u201cVector\u201d, Koltsovo, 630559 Novosibirsk Region, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1823-9701","authenticated-orcid":false,"given":"Denis V.","family":"Antonets","sequence":"additional","affiliation":[{"name":"State Research Center of Virology and Biotechnology \u201cVector\u201d, Koltsovo, 630559 Novosibirsk Region, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina A.","family":"Volosnikova","sequence":"additional","affiliation":[{"name":"State Research Center of Virology and Biotechnology \u201cVector\u201d, Koltsovo, 630559 Novosibirsk Region, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris N.","family":"Zaitsev","sequence":"additional","affiliation":[{"name":"State Research Center of Virology and Biotechnology \u201cVector\u201d, Koltsovo, 630559 Novosibirsk Region, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasiya Yu.","family":"Bakulina","sequence":"additional","affiliation":[{"name":"State Research Center of Virology and Biotechnology \u201cVector\u201d, Koltsovo, 630559 Novosibirsk Region, Russia"},{"name":"Department of Natural Sciences, Novosibirsk State University, 630090 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aliya G.","family":"Venyaminova","sequence":"additional","affiliation":[{"name":"Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences, 630090 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander A.","family":"Ilyichev","sequence":"additional","affiliation":[{"name":"State Research Center of Virology and Biotechnology \u201cVector\u201d, Koltsovo, 630559 Novosibirsk Region, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergei I.","family":"Bazhan","sequence":"additional","affiliation":[{"name":"State Research Center of Virology and Biotechnology \u201cVector\u201d, Koltsovo, 630559 Novosibirsk Region, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.clim.2016.10.016","article-title":"Ebola virus vaccines: Where do we stand?","volume":"173","author":"Pavot","year":"2016","journal-title":"Clin. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Pyankov, O.V., Setoh, Y.X., Bodnev, S.A., Edmonds, J.H., Pyankova, O.G., Pyankov, S.A., Pali, G., Belford, S., Lu, L., and La, M. (2017). Successful post-exposure prophylaxis of Ebola infected non-human primates using Ebola glycoprotein-specific equine IgG. Sci. Rep., 7.","DOI":"10.1038\/srep41537"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"6233","DOI":"10.3390\/v7122934","article-title":"Identification of a new ribonucleoside inhibitor of ebola virus replication","volume":"7","author":"Reynard","year":"2015","journal-title":"Viruses"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1586\/14760584.2014.885841","article-title":"Ebola virus vaccines: An overview of current approaches","volume":"13","author":"Marzi","year":"2014","journal-title":"Expert Rev. Vaccines"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/S0140-6736(16)32621-6","article-title":"Efficacy and effectiveness of an rVSV-vectored vaccine in preventing Ebola virus disease: Final results from the Guinea ring vaccination, open-label, cluster-randomised trial (Ebola \u00c7a Suffit!)","volume":"389","author":"Camacho","year":"2017","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1126\/science.aab3920","article-title":"VSV-EBOV rapidly protects macaques against infection with the 2014\/15 Ebola virus outbreak strain","volume":"349","author":"Marzi","year":"2015","journal-title":"Science"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1093\/infdis\/jix592","article-title":"Modified mRNA-Based Vaccines Elicit Robust Immune Responses and Protect Guinea Pigs from Ebola Virus Disease","volume":"217","author":"Meyer","year":"2018","journal-title":"J. Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"E4133","DOI":"10.1073\/pnas.1600299113","article-title":"Dendrimer-RNA nanoparticles generate protective immunity against lethal ebola, H1N1 influenza and Toxoplasma gondii challenges with a single dose","volume":"113","author":"Chahal","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1080\/21645515.2016.1238535","article-title":"Safety and immunogenicity of GamEvac-Combi, a heterologous VSV- and Ad5-vectored Ebola vaccine: An open phase I\/II trial in healthy adults in Russia","volume":"13","author":"Dolzhikova","year":"2017","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1038\/nm.2447","article-title":"CD8 + cellular immunity mediates rAd5 vaccine protection against Ebola virus infection of nonhuman primates","volume":"17","author":"Sullivan","year":"2011","journal-title":"Nat. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1893","DOI":"10.1073\/pnas.1209591110","article-title":"Antibodies are necessary for rVSV\/ZEBOV-GP-mediated protection against lethal Ebola virus challenge in nonhuman primates","volume":"110","author":"Marzi","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Rahim, M.N., Wee, E.G., He, S., Audet, J., Tierney, K., Moyo, N., Hannoun, Z., Crook, A., Baines, A., and Korber, B. (2019). Complete protection of the BALB\/c and C57BL\/6J mice against Ebola and Marburg virus lethal challenges by pan-filovirus T-cell epigraph vaccine. PLoS Pathog., 15.","DOI":"10.1371\/journal.ppat.1007564"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"E7578","DOI":"10.1073\/pnas.1806200115","article-title":"Analysis of CD8+ T cell response during the 2013\u20132016 Ebola epidemic in West Africa","volume":"115","author":"Sakabe","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Bazhan, S.I., Antonets, D.V., Karpenko, L.I., Oreshkova, S.F., Kaplina, O.N., Starostina, E.V., Dudko, S.G., Fedotova, S.A., and Ilyichev, A.A. (2019). In silico Designed Ebola Virus T-Cell Multi-Epitope DNA Vaccine Constructions Are Immunogenic in Mice. Vaccines, 7.","DOI":"10.3390\/vaccines7020034"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.4161\/hv.21873","article-title":"A multiagent filovirus DNA vaccine delivered by intramuscular electroporation completely protects mice from ebola and Marburg virus challenge","volume":"8","author":"Badger","year":"2012","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.coi.2011.03.008","article-title":"Electroporation delivery of DNA vaccines: Prospects for success","volume":"23","author":"Sardesai","year":"2011","journal-title":"Curr. Opin. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.cobme.2018.09.005","article-title":"Polymeric nucleic acid delivery for immunoengineering","volume":"7","author":"Tzeng","year":"2018","journal-title":"Curr. Opin. Biomed. Eng."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"D405","DOI":"10.1093\/nar\/gku938","article-title":"The immune epitope database (IEDB) 3.0","volume":"43","author":"Vita","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Antonets, D.V., and Bazhan, S.I. (2013). PolyCTLDesigner: A computational tool for constructing polyepitope T-cell antigens. BMC Res. Notes, 6.","DOI":"10.1186\/1756-0500-6-407"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1134\/S0026893310010152","article-title":"TEpredict: Software for T-Cell epitope prediction","volume":"44","author":"Antonets","year":"2010","journal-title":"Mol. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1007\/978-1-61779-564-0_15","article-title":"In silico design of functional DNA constructs","volume":"Volume 852","author":"Villalobos","year":"2012","journal-title":"Methods in Molecular Biology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/0968-4328(94)90051-5","article-title":"Negative staining: A brief assessment of current technical benefits, limitations and future possibilities","volume":"25","author":"Horne","year":"1994","journal-title":"Micron"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1007\/BF02759674","article-title":"Design of virus-like particles, exposing HIV-1 epitopes","volume":"34","author":"Lebedev","year":"2000","journal-title":"Mol. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/S0264-410X(02)00406-1","article-title":"Construction of artificial virus-like particles exposing HIV epitopes and the study of their immunogenic properties","volume":"21","author":"Karpenko","year":"2003","journal-title":"Vaccine"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/j.molimm.2007.07.016","article-title":"A synergistic effect of a combined bivalent DNA-protein anti-HIV-1 vaccine containing multiple T- and B-cell epitopes of HIV-1 proteins","volume":"45","author":"Bazhan","year":"2008","journal-title":"Mol. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1134\/S1068162020030073","article-title":"Study on the Methods for Synthesis of GM-CSF Conjugates with Alendronic Acid","volume":"46","author":"Esina","year":"2020","journal-title":"Russ. J. Bioorg. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4312","DOI":"10.1016\/j.vaccine.2007.02.058","article-title":"Combined virus-like particle-based polyepitope DNA\/protein HIV-1 vaccine\u2014Design, immunogenicity and toxicity studies","volume":"25","author":"Karpenko","year":"2007","journal-title":"Vaccine"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1134\/S1068162016020060","article-title":"Results of phase I clinical trials of a combined vaccine against HIV-1 based on synthetic polyepitope immunogens","volume":"42","author":"Karpenko","year":"2016","journal-title":"Russ. J. Bioorg. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"De Ara\u00fajo, R.V., da Silva Santos, S., Ferreira, E.I., and Giarolla, J. (2018). New advances in general biomedical applications of PAMAM dendrimers. Molecules, 23.","DOI":"10.3390\/molecules23112849"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.apmt.2018.05.002","article-title":"PAMAM dendrimers as efficient drug and gene delivery nanosystems for cancer therapy","volume":"12","author":"Dehghan","year":"2018","journal-title":"Appl. Mater. Today"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Dzmitruk, V., Apartsin, E., Ihnatsyeu-Kachan, A., Abashkin, V., Shcharbin, D., and Bryszewska, M. (2018). Dendrimers show promise for siRNA and microrna therapeutics. Pharmaceutics, 10.","DOI":"10.3390\/pharmaceutics10030126"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Knauer, N., Pashkina, E., and Apartsin, E. (2019). Topological aspects of the design of nanocarriers for therapeutic peptides and proteins. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11020091"},{"key":"ref_33","unstructured":"Sampathkumar, S.-G., and Yarema, K.J. (2007). Dendrimers in Cancer Treatment and Diagnosis. Nanotechnologies for the Life Sciences, Wiley-VCH Verlag GmbH & Co. KGaA."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Wang, X., Dai, Y., Zhao, S., Tang, J., Li, H., Xing, Y., Qu, G., Li, X., Dai, J., and Zhu, Y. (2014). PAMAM-Lys, a novel vaccine delivery vector, enhances the protective effects of the SjC23 DNA vaccine against schistosoma japonicum infection. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0086578"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"7452","DOI":"10.1158\/0008-5472.CAN-11-1766","article-title":"Peptide-conjugated PAMAM dendrimer as a universal DNA vaccine platform to target antigen-presenting cells","volume":"71","author":"Daftarian","year":"2011","journal-title":"Cancer Res."},{"key":"ref_36","first-page":"1535","article-title":"Pre-clinical and behavioural toxicity profile of PAMAM dendrimers in mice","volume":"466","author":"Chauhan","year":"2010","journal-title":"Proc. R. Soc. A Math. Phys. Eng. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1021\/mp300391v","article-title":"In vivo distribution and toxicity of PAMAM dendrimers in the central nervous system depend on their surface chemistry","volume":"10","author":"Albertazzi","year":"2013","journal-title":"Mol. Pharm."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1093\/infdis\/jiy537","article-title":"Protective Efficacy and Long-Term Immunogenicity in Cynomolgus Macaques by Ebola Virus Glycoprotein Synthetic DNA Vaccines","volume":"219","author":"Patel","year":"2019","journal-title":"J. Infect. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1128\/CVI.00162-06","article-title":"A DNA vaccine for Ebola virus is safe and immunogenic in a phase I clinical trial","volume":"13","author":"Martin","year":"2006","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Wang, S., and Lu, S. (2013). DNA immunization. Curr. Protoc. Microbiol.","DOI":"10.1002\/9780471729259.mc1803s31"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Zukancic, D., Suys, E.J.A., Pilkington, E.H., Algarni, A., Al-Wassiti, H., and Truong, N.P. (2020). The importance of poly(Ethylene glycol) and lipid structure in targeted gene delivery to lymph nodes by lipid nanoparticles. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12111068"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/S1461-5347(00)00273-X","article-title":"The use of PAMAM dendrimers in the efficient transfer of genetic material into cells","volume":"3","author":"Eichman","year":"2000","journal-title":"Pharm. Sci. Technol. Today"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1177\/1535370216643771","article-title":"Micro- and nanoparticulates for DNA vaccine delivery","volume":"241","author":"Farris","year":"2016","journal-title":"Exp. Biol. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1586\/14760584.2016.1141054","article-title":"Enhancing dendritic cell activation and HIV vaccine effectiveness through nanoparticle vaccination","volume":"15","author":"Glass","year":"2016","journal-title":"Expert Rev. Vaccines"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jcis.2012.11.061","article-title":"Re-considering how particle size and other properties of antigen-adjuvant complexes impact on the immune responses","volume":"395","author":"Yan","year":"2013","journal-title":"J. Colloid Interface Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1208\/s12248-012-9418-6","article-title":"Biodegradable particles as vaccine delivery systems: Size matters","volume":"15","author":"Joshi","year":"2013","journal-title":"AAPS J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.mattod.2015.06.003","article-title":"PAMAM dendrimers as promising nanocarriers for RNAi therapeutics","volume":"18","author":"Kesharwani","year":"2015","journal-title":"Mater. Today"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cis.2018.06.005","article-title":"PAMAM dendrimer\u2014Cell membrane interactions","volume":"257","author":"Fox","year":"2018","journal-title":"Adv. Colloid Interface Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2461","DOI":"10.1021\/bc200275g","article-title":"Structurally flexible triethanolamine core pamam dendrimers are effective nanovectors for DNA transfection in vitro and in vivo to the mouse thymus","volume":"22","author":"Liu","year":"2011","journal-title":"Bioconjugate Chem."}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/8\/4\/718\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:40:18Z","timestamp":1760179218000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/8\/4\/718"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,1]]},"references-count":49,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["vaccines8040718"],"URL":"https:\/\/doi.org\/10.3390\/vaccines8040718","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,1]]}}}