Tissue distribution of a plasmid DNA encoding Hsp65 gene is dependent on the dose administered through intramuscular delivery

dc.contributorUniversidade Estadual Paulista (UNESP)
dc.creatorCoelho-Castelo, A. A M
dc.creatorTrombone, A. P.
dc.creatorRosada, R. S.
dc.creatorSantos, R. R.
dc.creatorBonato, V. L D
dc.creatorSartori, A.
dc.creatorSilva, C. L.
dc.date2014-05-27T11:21:48Z
dc.date2016-10-25T18:21:55Z
dc.date2014-05-27T11:21:48Z
dc.date2016-10-25T18:21:55Z
dc.date2006-01-30
dc.date.accessioned2017-04-06T01:17:43Z
dc.date.available2017-04-06T01:17:43Z
dc.identifierGenetic Vaccines and Therapy, v. 4.
dc.identifier1479-0556
dc.identifierhttp://hdl.handle.net/11449/68766
dc.identifierhttp://acervodigital.unesp.br/handle/11449/68766
dc.identifier10.1186/1479-0556-4-1
dc.identifier2-s2.0-33645016634.pdf
dc.identifier2-s2.0-33645016634
dc.identifierhttp://dx.doi.org/10.1186/1479-0556-4-1
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/890083
dc.descriptionIn order to assess a new strategy of DNA vaccine for a more complete understanding of its action in immune response, it is important to determine the in vivo biodistribution fate and antigen expression. In previous studies, our group focused on the prophylactic and therapeutic use of a plasmid DNA encoding the Mycobacterium leprae 65-kDa heat shock protein (Hsp65) and achieved an efficient immune response induction as well as protection against virulent M. tuberculosis challenge. In the present study, we examined in vivo tissue distribution of naked DNA-Hsp65 vaccine, the Hsp65 message, genome integration and methylation status of plasmid DNA. The DNA-Hsp65 was detectable in several tissue types, indicating that DNA-Hsp65 disseminates widely throughout the body. The biodistribution was dose-dependent. In contrast, RT-PCR detected the Hsp65 message for at least 15 days in muscle or liver tissue from immunized mice. We also analyzed the methylation status and integration of the injected plasmid DNA into the host cellular genome. The bacterial methylation pattern persisted for at least 6 months, indicating that the plasmid DNA-Hsp65 does not replicate in mammalian tissue, and Southern blot analysis showed that plasmid DNA was not integrated. These results have important implications for the use of DNA-Hsp65 vaccine in a clinical setting and open new perspectives for DNA vaccines and new considerations about the inoculation site and delivery system. © 2006 Coelho-Castelo et al; licensee BioMed Central Ltd.
dc.languageeng
dc.relationGenetic Vaccines and Therapy
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectDNA vaccine
dc.subjectheat shock protein 65
dc.subjectplasmid DNA
dc.subjectanimal experiment
dc.subjectanimal tissue
dc.subjectcontrolled study
dc.subjectDNA isolation
dc.subjectDNA methylation
dc.subjectdose response
dc.subjectdrug distribution
dc.subjectgenome
dc.subjectimmunization
dc.subjectin vivo study
dc.subjectliver
dc.subjectmouse
dc.subjectmuscle tissue
dc.subjectnonhuman
dc.subjectreverse transcription polymerase chain reaction
dc.subjectRNA isolation
dc.subjectSouthern blotting
dc.subjecttissue distribution
dc.subjectviral gene delivery system
dc.subjectAnimalia
dc.subjectBacteria (microorganisms)
dc.subjectMammalia
dc.subjectMycobacterium leprae
dc.titleTissue distribution of a plasmid DNA encoding Hsp65 gene is dependent on the dose administered through intramuscular delivery
dc.typeOtro


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