title: Homologous prime-boost strategy with TgPI-1 improves the immune response and protects highly susceptible mice against chronic Toxoplasma gondii infection.
abstract: Subunit-based vaccines are safer than live or attenuated pathogen vaccines, although they are generally weak immunogens. Thus, proper combination of immunization strategies and adjuvants are needed to increase their efficacy. We have previously protected C3H/HeN mice from Toxoplasma gondii infection by immunization with the serine protease inhibitor-1 (TgPI-1) in combination with alum. In this work, we explore an original vaccination protocol that combines administration of recombinant TgPI-1 by intradermal and intranasal routes in order to enhance protection in the highly susceptible C57BL/6 strain. Mice primed intradermally with rTgPI-1 plus alum and boosted intranasally with rTgPI-1 plus CpG-ODN elicited a strong specific Th1/Th2 humoral response, along with a mucosal immune response characterized by specific-IgA in intestinal lavages. A positive cellular response of mesentheric lymph node cells and Th1/Th2 cytokine secretion in the ileon were also detected. When immunized mice were challenged with the cystogenic Me49 T. gondii strain, they displayed up to 62% reduction in brain parasite burden. Moreover, adoptive transfer of mesenteric lymph node cells from vaccinated to naïve mice induced significant protection against infection. These results demonstrate that this strategy that combines the administration of TgPI-1 by two different routes, intradermal priming and intranasal boost, improves protective immunity against T. gondii chronic infection in highly susceptible mice.
authors.affiliation: Laboratorio de Inmunología, Vacunas y Alergia, Centro de Salud y Medio Ambiente (CESyMA), Escuela de Ciencia y Tecnología (ECyT), Universidad Nacional de San Martín, Argentina.
authors.forename: Vanesa R
authors.initials: VR
authors.lastname: Sánchez
authors.affiliation: Laboratorio de Inmunología, Vacunas y Alergia, Centro de Salud y Medio Ambiente (CESyMA), Escuela de Ciencia y Tecnología (ECyT), Universidad Nacional de San Martín, Argentina.
authors.forename: Ignacio M
authors.initials: IM
authors.lastname: Fenoy
authors.affiliation: Laboratorio de Inmunología, Vacunas y Alergia, Centro de Salud y Medio Ambiente (CESyMA), Escuela de Ciencia y Tecnología (ECyT), Universidad Nacional de San Martín, Argentina.
authors.forename: Mariano S
authors.initials: MS
authors.lastname: Picchio
authors.affiliation: Laboratorio de Inmunología, Vacunas y Alergia, Centro de Salud y Medio Ambiente (CESyMA), Escuela de Ciencia y Tecnología (ECyT), Universidad Nacional de San Martín, Argentina.
authors.forename: Ariadna S
authors.initials: AS
authors.lastname: Soto
authors.affiliation: Laboratorio de Inmunología, Vacunas y Alergia, Centro de Salud y Medio Ambiente (CESyMA), Escuela de Ciencia y Tecnología (ECyT), Universidad Nacional de San Martín, Argentina.
authors.forename: Nadia
authors.initials: N
authors.lastname: Arcon
authors.affiliation: Laboratorio de Inmunología, Vacunas y Alergia, Centro de Salud y Medio Ambiente (CESyMA), Escuela de Ciencia y Tecnología (ECyT), Universidad Nacional de San Martín, Argentina.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Goldman
authors.affiliation: Laboratorio de Inmunología, Vacunas y Alergia, Centro de Salud y Medio Ambiente (CESyMA), Escuela de Ciencia y Tecnología (ECyT), Universidad Nacional de San Martín, Argentina. Electronic address: vmartin@unsam.edu.ar.
authors.forename: Valentina
authors.initials: V
authors.lastname: Martin
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000281:Administration, Intranasal; D000534:Alum Compounds / Q000008:administration & dosage; D000818:Animals; D004334:Drug Administration Schedule; D005260:Female; D018928:Immunity, Mucosal; D007279:Injections, Subcutaneous; D051379:Mice; D008810:Mice, Inbred C57BL; D015800:Protozoan Proteins / Q000008:administration & dosage*; D016052:Protozoan Vaccines / Q000276:immunology*; D014122:Toxoplasma / Q000276:immunology*; D014124:Toxoplasmosis, Animal / Q000276:immunology / Q000517:prevention & control*; D014611:Vaccination
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; C412510:TgPI protein, Toxoplasma gondii; C041524:aluminum sulfate
keywords: Mucosal immunity; Prime-boost strategy; Serin protease inhibitor-1; Subunit vaccine; Toxoplasma gondii