A bivalent recombinant mycobacterium bovis BCG expressing the S1 subunit of the pertussis toxin induces a polyfunctional CD4+ T cell immune response

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dc.contributorLaboratório Especial de Desenvolvimento de Vacinas (LEDV)pt_BR
dc.contributor.authorKanno, Alex Issamupt_BR
dc.contributor.authorGoulart, Cibellypt_BR
dc.contributor.authorLeite, Luciana Cezar de Cerqueirapt_BR
dc.contributor.authorPagliarone, Ana Carolinapt_BR
dc.contributor.authorNascimento, Ivan Pereirapt_BR
dc.identifier.citationKanno AI, Goulart C, Leite LCC, Pagliarone AC, Nascimento IP. A bivalent recombinant mycobacterium bovis BCG expressing the S1 subunit of the pertussis toxin induces a polyfunctional CD4+ T cell immune response. Biomed Res Int. 2019;2019:9630793. doi:10.1155/2019/9630793.pt_BR
dc.description.abstractBackground. A recombinant BCG strain expressing the genetically detoxified S1 subunit of pertussis toxin 9K/129G (rBCG-S1PT), previously constructed by our research group, demonstrated the ability to develop high protection in mouse models of pertussis challenge which correlated with the induction of a Th1 immune response pattern. The Th1 immune response induced by rBCG-S1PT treatment was also confirmed in the murine orthotopic bladder cancer model, in which the intravesical instillation of rBCG-S1PT resulted in an improved antitumor effect. Based on these observations, we hypothesize that the reengineering of the S1PT expression in BCG could increase the efficiency of the protective Th1 immune response in order to develop a new alternative of immunotherapy in bladder cancer treatment. Objectives. To construct rBCG strains expressing S1PT from extrachromosomal (rBCG-S1PT) and integrative vectors (rBCG-Sli), or their combination, generating the bivalent strain (rBCG-S1+S1i), and to evaluate the respective immunogenicity of rBCG strains in mice. Methods. Mycobacterial plasmids were constructed by cloning the s1pt gene under integrative and extrachromosomal vectors and used to transform BCG, individually or in combination. Antigen expression and localization were confirmed by Western blot. Mice were immunized with wild-type BCG or the rBCG strains, and cytokines quantification and flow cytometry analysis were performed in splenocytes culture stimulated with mycobacterial-specific proteins. Findings. S1PT expression was confirmed in all rBCG strains. The extrachromosomal vector directs S1PT to the cell wall-associated fraction, while the integrative vector directs its expression mainly to the intracellular fraction. Higher levels of IFN-? were observed in the splenocytes culture from the group immunized with rBCG-S1i in comparison to BCG or rBCG-S1PT. rBCG-S1+S1i showed higher levels of CD4+ IFN-?+ and double-positive CD4+ IFN-?+ TNF-a+ T cells. Conclusions. rBCG-S1+S1i was able to express the two forms of S1PT and elicited higher induction of polyfunctional CD4+ T cells, indicating enhanced immunogenicity and suggesting its use as immunotherapy for bladder cancer.pt_BR
dc.description.sponsorshipBanco Nacional de Desenvolvimento Econômico e Social (BNDES)pt_BR
dc.description.sponsorshipFundação Butantanpt_BR
dc.relation.ispartofBioMed Research Internationalpt_BR
dc.rightsOpen Accesspt_BR
dc.titleA bivalent recombinant mycobacterium bovis BCG expressing the S1 subunit of the pertussis toxin induces a polyfunctional CD4+ T cell immune responsept_BR
dc.relation.ispartofabbreviatedBiomed Res Intpt_BR
dc.identifier.citationabntv. 2019, 9630793, 2019pt_BR
dc.contributor.butantanGoulart, Cibelly|:Aluno|:Laboratório Especial de Desenvolvimento de Vacinas (LEDV)|:pt_BR
dc.contributor.butantanLeite, Luciana Cezar de Cerqueira|:Pesquisador|:Laboratório Especial de Desenvolvimento de Vacinas (LEDV)|:pt_BR
dc.contributor.butantanPagliarone, Ana Carolina|:Colaborador|:Laboratório Especial de Desenvolvimento de Vacinas (LEDV)|:pt_BR
dc.contributor.butantanNascimento, Ivan Pereira|:Pesquisador|:Laboratório Especial de Desenvolvimento de Vacinas (LEDV)|:Autor de correspondênciapt_BR
dc.contributor.butantanKanno, Alex Issamu|:Aluno|:Laboratório Especial de Desenvolvimento de Vacinas (LEDV)|:PrimeiroAutorpt_BR
dc.sponsorship.butantanBanco Nacional de Desenvolvimento Econômico e Social (BNDES)¦¦pt_BR
dc.sponsorship.butantanFundação Butantan¦¦pt_BR
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