Cellular immune response induced by dna immunization of mice with drug resistant integrases of hiv-1 clade a offers partial protection against growth and metastatic activity of integrase-expressing adenocarcinoma cells

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dc.contributor.authorIsaguliants, Maria
dc.contributor.authorKrotova, Olga
dc.contributor.authorPetkov, Stefan
dc.contributor.authorJansons, Juris
dc.contributor.authorBayurova, Ekaterina
dc.contributor.authorMezale, Dzeina
dc.contributor.authorFridrihsone, Ilze
dc.contributor.authorKilpelainen, Athina
dc.contributor.authorPodschwadt, Philip
dc.contributor.authorAgapkina, Yulia
dc.contributor.authorSmirnova, Olga
dc.contributor.authorKostic, Linda
dc.contributor.authorSaleem, Mina
dc.contributor.authorLatyshev, Oleg
dc.contributor.authorEliseeva, Olesja
dc.contributor.authorMalkova, Anastasia
dc.contributor.authorGorodnicheva, Tatiana
dc.contributor.authorWahren, Britta
dc.contributor.authorGordeychuk, Ilya
dc.contributor.authorStarodubova, Elizaveta
dc.contributor.authorLatanova, Anastasia
dc.contributor.institutionResearch Department
dc.date.accessioned2022-01-26T13:35:01Z
dc.date.available2022-01-26T13:35:01Z
dc.date.issued2021-06
dc.descriptionFunding Information: Funding: Experiments were supported by the grants of the Russian Science Fund 15-15-30039, Russian Fund for Basic Research 20-04-01034, Latvian Science Fund LZP 2018-2-03-08, and EU-ROPARTNER project “Strengthening and spreading international partnership activities of the Faculty of Biology and Environmental Protection of University of Lodz, Poland, for interdisciplinary research and innovation”. Mobility and method acquisition were supported by Swedish institute PI project 19806/2016TP, and Horizon 2020 project VACTRAIN#692293. MI and BW were supported by Horizon 2020 grant EAVI contract N68113. Funding Information: Experiments were supported by the grants of the Russian Science Fund 15-15-30039, Russian Fund for Basic Research 20-04-01034, Latvian Science Fund LZP 2018-2-03-08, and EU-ROPARTNER project ?Strengthening and spreading international partnership activities of the Faculty of Biology and Environmental Protection of University of Lodz, Poland, for interdisciplinary research and innovation?. Mobility and method acquisition were supported by Swedish institute PI project 19806/2016TP, and Horizon 2020 project VACTRAIN#692293. MI and BW were supported by Horizon 2020 grant EAVI contract N68113. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
dc.description.abstractTherapeutic DNA-vaccination against drug-resistant HIV-1 may hinder emergence and spread of drug-resistant HIV-1, allowing for longer successful antiretroviral treatment (ART) up-to relief of ART. We designed DNA-vaccines against drug-resistant HIV-1 based on consensus clade A integrase (IN) resistant to raltegravir: IN_in_r1 (L74M/E92Q/V151I/N155H/G163R) or IN_in_r2 (E138K/G140S/Q148K) carrying D64V abrogating IN activity. INs, overexpressed in mammalian cells from synthetic genes, were assessed for stability, route of proteolytic degradation, and ability to induce oxidative stress. Both were found safe in immunotoxicity tests in mice, with no inherent carcinogenicity: their expression did not enhance tumorigenic or metastatic potential of adenocarcinoma 4T1 cells. DNA-immunization of mice with INs induced potent multicytokine T-cell response mainly against aa 209–239, and moderate IgG response cross-recognizing diverse IN variants. DNA-immunization with IN_in_r1 protected 60% of mice from challenge with 4Tlluc2 cells expressing non-mutated IN, while DNA-immunization with IN_in_r2 protected only 20% of mice, although tumor cells expressed IN matching the immunogen. Tumor size inversely correlated with IN-specific IFN-γ/IL-2 T-cell response. IN-expressing tumors displayed compromised metastatic activity restricted to lungs with reduced metastases size. Protective potential of IN immunogens relied on their immunogenicity for CD8+ T-cells, dependent on proteasomal processing and low level of oxidative stress.en
dc.description.statusPeer reviewed
dc.format.extent19767722
dc.identifier.citationIsaguliants, M, Krotova, O, Petkov, S, Jansons, J, Bayurova, E, Mezale, D, Fridrihsone, I, Kilpelainen, A, Podschwadt, P, Agapkina, Y, Smirnova, O, Kostic, L, Saleem, M, Latyshev, O, Eliseeva, O, Malkova, A, Gorodnicheva, T, Wahren, B, Gordeychuk, I, Starodubova, E & Latanova, A 2021, 'Cellular immune response induced by dna immunization of mice with drug resistant integrases of hiv-1 clade a offers partial protection against growth and metastatic activity of integrase-expressing adenocarcinoma cells', Microorganisms, vol. 9, no. 6, 1219. https://doi.org/10.3390/microorganisms9061219
dc.identifier.doi10.3390/microorganisms9061219
dc.identifier.urihttps://dspace.rsu.lv/jspui/handle/123456789/7301
dc.identifier.urlhttp://www.scopus.com/inward/record.url?scp=85107376689&partnerID=8YFLogxK
dc.language.isoeng
dc.relation.ispartofMicroorganisms
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectAntibodies
dc.subjectART
dc.subjectHIV-1
dc.subjectImmunotoxicity
dc.subjectIntegrase
dc.subjectLentiviral transduction
dc.subjectMetastasis
dc.subjectMurine adenocarcinoma 4T1luc2 cells
dc.subjectResistance to tumor growth
dc.subjectT-cell response
dc.subjectTherapeutic DNA vaccine
dc.subjectTumor growth
dc.subject3.1 Basic medicine
dc.subject3.2 Clinical medicine
dc.subject1.6 Biological sciences
dc.subject1.1. Scientific article indexed in Web of Science and/or Scopus database
dc.subjectMicrobiology
dc.subjectMicrobiology (medical)
dc.subjectVirology
dc.subjectSDG 3 - Good Health and Well-being
dc.titleCellular immune response induced by dna immunization of mice with drug resistant integrases of hiv-1 clade a offers partial protection against growth and metastatic activity of integrase-expressing adenocarcinoma cellsen
dc.type/dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article

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