title: Enhancement of the protective efficacy of a ROP18 vaccine against chronic toxoplasmosis by nasal route.
abstract: Infection with the parasite Toxoplasma gondii causes serious public health problems and is of great economic importance worldwide. No vaccine is currently available, so the design of efficient vaccine strategies is still a topical question. In this study, we evaluated the immunoprophylactic potential of a T. gondii virulence factor, the rhoptry kinase ROP18, in a mouse model of chronic toxoplasmosis: first using a recombinant protein produced in Schneider insect cells adjuvanted with poly I:C emulsified in Montanide SV71 by a parenteral route or adjuvanted with cholera toxin by the nasal route and second using a DNA plasmid encoding ROP18 adjuvanted with GM-CSF ± IL-12 DNA. If both intranasal and subcutaneous recombinant ROP18 immunizations induced predominantly anti-ROP18 IgG1 antibodies and generated a mixed systemic Th1-/Th2-type cellular immune response characterized by the production of IFN-γ, IL-2, Il-10 and IL-5, only intranasal vaccination induced a mucosal (IgA) humoral response in intestinal washes associated with a significant brain cyst reduction (50 %) after oral challenge with T. gondii cysts. DNA immunization induced antibodies and redirected the cellular immune response toward a Th1-type response (production of IFN-γ and IL-2) but did not confer protection. These results suggest that ROP18 could be a component of a subunit vaccine against toxoplasmosis and that strategies designed to enhance mucosal protective immune responses could lead to more encouraging results.
authors.affiliation: ISP, INRA, Université de Tours, UMR 1282, 37380, Nouzilly, France.
authors.forename: Imran
authors.initials: I
authors.lastname: Rashid
authors.affiliation: ISP, INRA, Université de Tours, UMR 1282, 37380, Nouzilly, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Moiré
authors.affiliation: ISP, INRA, Université de Tours, UMR 1282, 37380, Nouzilly, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Héraut
authors.affiliation: ISP, INRA, Université de Tours, UMR 1282, 37380, Nouzilly, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Dimier-Poisson
authors.affiliation: ISP, INRA, Université de Tours, UMR 1282, 37380, Nouzilly, France. mevelec@univ-tours.fr.
authors.forename: Marie-Noëlle
authors.initials: MN
authors.lastname: Mévélec
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000281:Administration, Intranasal; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D002772:Cholera Toxin / Q000008:administration & dosage; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000097:blood; D007279:Injections, Subcutaneous; D008808:Mice, Inbred CBA; D009829:Oleic Acids / Q000008:administration & dosage; D011070:Poly I-C / Q000008:administration & dosage; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000276:immunology*; D015800:Protozoan Proteins; D016052:Protozoan Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014123:Toxoplasmosis / Q000517:prevention & control*; D016896:Treatment Outcome; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D016207:Cytokines; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D009829:Oleic Acids; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; D011994:Recombinant Proteins; D019444:Vaccines, DNA; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; D002772:Cholera Toxin; D017346:Protein Serine-Threonine Kinases; C556793:ROP18 protein, Toxoplasma gondii; D011070:Poly I-C
keywords: Immunoprophylaxis; Mucosal route; ROP18; T. gondii