Novel Adjuvant Based on the Pore-Forming Protein Sticholysin II Encapsulated into Liposomes Effectively Enhances the Antigen-Specific CTL-Mediated Immune Response

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dc.citation.issue7
dc.citation.volume198
dc.contributor.authorLaborde, Rady J.
dc.contributor.authorSanchez-Ferras, Oraly
dc.contributor.authorLuzardo, Maria C.
dc.contributor.authorCruz-Leal, Yoelys
dc.contributor.authorFernandez, Audry
dc.contributor.authorMesa, Circe
dc.contributor.authorOliver, Liliana
dc.contributor.authorCanet, Liem
dc.contributor.authorAbreu-Butin, Liane [UNIFESP]
dc.contributor.authorNogueira, Catarina V.
dc.contributor.authorTejuca, Mayra
dc.contributor.authorPazos, Fabiola
dc.contributor.authorAlvarez, Carlos
dc.contributor.authorAlonso, Maria E.
dc.contributor.authorLongo-Maugeri, Ieda M. [UNIFESP]
dc.contributor.authorStarnbach, Michael N.
dc.contributor.authorHiggins, Darren E.
dc.contributor.authorFernandez, Luis E.
dc.contributor.authorLanio, Maria E.
dc.coverageBethesda
dc.date.accessioned2020-07-17T14:02:34Z
dc.date.available2020-07-17T14:02:34Z
dc.date.issued2017
dc.description.abstractVaccine strategies to enhance CD8(+) CTL responses remain a current challenge because they should overcome the plasmatic and endosomal membranes for favoring exogenous Ag access to the cytosol of APCs. As a way to avoid this hurdle, sticholysin (St) II, a pore-forming protein from the Caribbean Sea anemone Stichodactyla helianthus, was encapsulated with OVA into liposomes (Lp/OVA/StII) to assess their efficacy to induce a CTL response. OVA-specific CD8(+) T cells transferred to mice immunized with Lp/OVA/StII experienced a greater expansion than when the recipients were injected with the vesicles without St, mostly exhibiting a memory phenotype. Consequently, Lp/OVA/StII induced a more potent effector function, as shown by CTLs, in vivo assays. Furthermore, treatment of E.G7-OVA tumor-bearing mice with Lp/OVA/StII significantly reduced tumor growth being more noticeable in the preventive assay. The contribution of CD4(+) and CD8(+) T cells to CTL and antitumor activity, respectively, was elucidated. Interestingly, the irreversibly inactive variant of the StI mutant StI W111C, encapsulated with OVA into Lp, elicited a similar OVA-specific CTL response to that observed with Lp/OVA/StII or vesicles encapsulating recombinant StI or the reversibly inactive StI W111C dimer. These findings suggest the relative independence between StII pore-forming activity and its immunomodulatory properties. In addition, StII-induced in vitro maturation of dendritic cells might be supporting these properties. These results are the first evidence, to our knowledge, that StII, a pore-forming protein from a marine eukaryotic organism, encapsulated into Lp functions as an adjuvant to induce a robust specific CTL response.en
dc.description.affiliationUniv Havana, Ctr Prot Studies, Fac Biol, Calle 25 Entre J & I,455,Plaza Revoluc, Havana 10400, Cuba
dc.description.affiliationCtr Mol Immunol, Immunobiol Div, Havana 11600, Cuba
dc.description.affiliationUniv Fed Sao Paulo, Paulista Med Sch, Dept Microbiol Immunol & Parasitol, Discipline Immunol, BR-04023900 Sao Paulo, Brazil
dc.description.affiliationHarvard Med Sch, Dept Microbiol & Immunobiol, Boston, MA 02115 USA
dc.description.affiliationMcGill Univ, Goodman Canc Res Ctr, Montreal, PQ, Canada
dc.description.affiliationMcGill Univ, Dept Biochem, Montreal, PQ, Canada
dc.description.affiliationUnifespUniv Fed Sao Paulo, Paulista Med Sch, Dept Microbiol Immunol & Parasitol, Discipline Immunol, BR-04023900 Sao Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipCenter of Molecular Immunology
dc.description.sponsorshipInternational Foundation for Science
dc.description.sponsorshipCAPES-MES
dc.description.sponsorshipIDCAPES-MES: 111/11
dc.format.extent2772-2784
dc.identifierhttp://dx.doi.org/10.4049/jimmunol.1600310
dc.identifier.citationJournal Of Immunology. Bethesda, v. 198, n. 7, p. 2772-2784, 2017.
dc.identifier.doi10.4049/jimmunol.1600310
dc.identifier.issn0022-1767
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/54870
dc.identifier.wosWOS:000397611900025
dc.language.isoeng
dc.publisherAmer Assoc Immunologists
dc.relation.ispartofJournal Of Immunology
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titleNovel Adjuvant Based on the Pore-Forming Protein Sticholysin II Encapsulated into Liposomes Effectively Enhances the Antigen-Specific CTL-Mediated Immune Responseen
dc.typeinfo:eu-repo/semantics/article
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