Pelizon, Ana [UNESP]Sartori, Alexandrina [UNESP]Martins, Douglas R. [UNESP]Zorzella, Sofia F.G. [UNESP]Trombone, Ana PaulaLorenzi, Júlio C.C.Carvalho, Robson F. [UNESP]Brandão, Izaíra T.Coelho-Castelo, Arlete A.M.Silva, Célio L.2014-05-272014-05-272007-11-29Genetic Vaccines and Therapy, v. 5.1479-0556http://hdl.handle.net/11449/69999Background: Vaccination of neonates is generally difficult due to the immaturity of the immune system and consequent higher susceptibility to tolerance induction. Genetic immunization has been described as an alternative to trigger a stronger immune response in neonates, including significant Th1 polarization. In this investigation we analysed the potential use of a genetic vaccine containing the heat shock protein (hsp65) from Mycobacterium leprae (pVAXhsp65) against tuberculosis (TB) in neonate mice. Aspects as antigen production, genomic integration and immunogenicity were evaluated. Methods: Hsp65 message and genomic integration were evaluated by RT-PCR and Southern blot, respectively. Immunogenicity of pVAXhsp65 alone or combined with BCG was analysed by specific induction of antibodies and cytokines, both quantified by ELISA. Results: This DNA vaccine was transcribed by muscular cells of neonate mice without integration into the cellular genome. Even though this vaccine was not strongly immunogenic when entirely administered (three doses) during early animal's life, it was not tolerogenic. In addition, pVAXhsp65 and BCG were equally able to prime newborn mice for a strong and mixed immune response (Th1 + Th2) to pVAXhsp65 boosters administered later, at the adult life. Conclusion: These results suggest that pVAXhsp65 can be safely used as a priming stimulus in neonate animals in prime-boost similar strategies to control TB. However, priming with BCG or pVAXhsp65, directed the ensuing immune response triggered by an heterologous or homologous booster, to a mixed Th1/Th2 pattern of response. Measures as introduction of IL-12 or GM-CSF genes in the vaccine construct or even IL-4 neutralization, are probably required to increase the priming towards Th1 polarization to ensure control of tuberculosis infection. © 2007 Pelizon et al; licensee BioMed Central Ltd.engbacterial proteinBCG vaccinegentamicinglutaminegranulocyte macrophage colony stimulating factorheat shock protein 65interleukin 12interleukin 4interleukin 5monoclonal antibodyanimal cellanimal experimentantibody productionBCG vaccinationcontrolled studycytokine productionDNA immunizationdrug safetyenzyme linked immunosorbent assaygene inductiongenetic immunizationimmune responseimmunogenicityimmunomodulationmouseMycobacterium lepraenewbornnonhumanreverse transcription polymerase chain reactionSouthern blottingTh1 cellTh2 celltuberculosis controlAnimaliaMusArtigo10.1186/1479-0556-5-12Acesso aberto2-s2.0-389491931972-s2.0-38949193197.pdf49775724161295270000-0002-4901-7714