title: Novel Adjuvant Based on the Pore-Forming Protein Sticholysin II Encapsulated into Liposomes Effectively Enhances the Antigen-Specific CTL-Mediated Immune Response.
abstract: Vaccine 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 anemoneStichodactyla 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.
authors.affiliation: Center for Protein Studies, Faculty of Biology, University of Havana, Havana 10400, Cuba.
authors.forename: Rady J
authors.identifier: 0000-0002-3227-2292
authors.initials: RJ
authors.lastname: Laborde
authors.affiliation: Center for Protein Studies, Faculty of Biology, University of Havana, Havana 10400, Cuba.
authors.forename: Oraly
authors.initials: O
authors.lastname: Sanchez-Ferras
authors.affiliation: Center for Protein Studies, Faculty of Biology, University of Havana, Havana 10400, Cuba.
authors.forename: María C
authors.initials: MC
authors.lastname: Luzardo
authors.affiliation: Center for Protein Studies, Faculty of Biology, University of Havana, Havana 10400, Cuba.
authors.forename: Yoelys
authors.initials: Y
authors.lastname: Cruz-Leal
authors.affiliation: Immunobiology Division, Center of Molecular Immunology, Havana 11600, Cuba.
authors.forename: Audry
authors.initials: A
authors.lastname: Fernández
authors.affiliation: Immunobiology Division, Center of Molecular Immunology, Havana 11600, Cuba.
authors.forename: Circe
authors.initials: C
authors.lastname: Mesa
authors.affiliation: Immunobiology Division, Center of Molecular Immunology, Havana 11600, Cuba.
authors.forename: Liliana
authors.identifier: 0000-0001-5308-7646
authors.initials: L
authors.lastname: Oliver
authors.affiliation: Center for Protein Studies, Faculty of Biology, University of Havana, Havana 10400, Cuba.
authors.forename: Liem
authors.initials: L
authors.lastname: Canet
authors.affiliation: Discipline of Immunology, Department of Microbiology, Immunology, and Parasitology, Paulista Medical School, Federal University of São Paulo, São Paulo 04023-900, Brazil; and.
authors.forename: Liane
authors.initials: L
authors.lastname: Abreu-Butin
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115.
authors.forename: Catarina V
authors.initials: CV
authors.lastname: Nogueira
authors.affiliation: Center for Protein Studies, Faculty of Biology, University of Havana, Havana 10400, Cuba.
authors.forename: Mayra
authors.initials: M
authors.lastname: Tejuca
authors.affiliation: Center for Protein Studies, Faculty of Biology, University of Havana, Havana 10400, Cuba.
authors.forename: Fabiola
authors.initials: F
authors.lastname: Pazos
authors.affiliation: Center for Protein Studies, Faculty of Biology, University of Havana, Havana 10400, Cuba.
authors.forename: Carlos
authors.initials: C
authors.lastname: Álvarez
authors.affiliation: Center for Protein Studies, Faculty of Biology, University of Havana, Havana 10400, Cuba.
authors.forename: María E
authors.initials: ME
authors.lastname: Alonso
authors.affiliation: Discipline of Immunology, Department of Microbiology, Immunology, and Parasitology, Paulista Medical School, Federal University of São Paulo, São Paulo 04023-900, Brazil; and.
authors.forename: Ieda M
authors.identifier: 0000-0003-4184-8414
authors.initials: IM
authors.lastname: Longo-Maugéri
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115.
authors.forename: Michael N
authors.initials: MN
authors.lastname: Starnbach
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115.
authors.forename: Darren E
authors.initials: DE
authors.lastname: Higgins
authors.affiliation: Immunobiology Division, Center of Molecular Immunology, Havana 11600, Cuba; mlanio@fbio.uh.cu luis@cim.sld.cu.
authors.forename: Luis E
authors.initials: LE
authors.lastname: Fernández
authors.affiliation: Center for Protein Studies, Faculty of Biology, University of Havana, Havana 10400, Cuba; mlanio@fbio.uh.cu luis@cim.sld.cu.
authors.forename: María E
authors.identifier: 0000-0002-1364-3713
authors.initials: ME
authors.lastname: Lanio
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology*; D003064:Cnidarian Venoms / Q000008:administration & dosage* / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D008081:Liposomes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000473:pathology*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D003064:Cnidarian Venoms; D008081:Liposomes; C404794:sticholysin II