title: N-terminal fusion of a toll-like receptor 2-ligand to a Neospora caninum chimeric antigen efficiently modifies the properties of the specific immune response.
abstract: Immunoprophylactic products against neosporosis during pregnancy should induce an appropriately balanced immune response. In this respect, OprI, a bacterial lipoprotein targeting toll like receptor (TLR)2, provides promising adjuvant properties. We report on the manipulation of the innate and the T-cell immune response through the fusion of OprI with the Neospora caninum chimeric protein Mic3-1-R. In contrast to Mic3-1-R, OprI-MIC3-1-R significantly activated bone-marrow dendritic cells from naïve mice. Mice immunized with OprI-Mic3-1-R induced an immune response with mixed T helper (Th)1 and Th2 properties (high levels of both immunoglobulin (Ig)G1 and IgG2a and of interleukin (IL)-10, IL-12(p70) and interferon-γ responses) whereas Mic3-1-R+saponin induced a clear Th2-biased response (low IgG2a and high IL-4 and IL-10). After mating and challenge with N. caninum, increased expression of interferon-γ was only found in placentas from OprI-Mic3-1-R immunized dams. However, no protection against vertical transmission and neonatal mortality was observed in either of the two groups. These results indicated that more exhaustive studies must be done to elucidate the immune mechanisms associated with transplacental transmission. Antigen linkage to TLR2-ligands, such as OprI, is a useful tool to investigate this enigma by reorienting the innate and adaptive immune responses against other candidate antigens in future studies.
authors.affiliation: Institute for Parasitology,Vetsuisse Faculty,University of Berne,Länggass-Strasse 122,CH-3012 Bern,Switzerland.
authors.forename: Adriana
authors.initials: A
authors.lastname: Aguado-Martínez
authors.affiliation: CIISA,Faculdade de Medicina Veterinária,ULisboa,Avenida da Universidade Técnica,1300-477 Lisboa,Portugal.
authors.forename: Afonso P
authors.initials: AP
authors.lastname: Basto
authors.affiliation: Institute for Parasitology,Vetsuisse Faculty,University of Berne,Länggass-Strasse 122,CH-3012 Bern,Switzerland.
authors.forename: Joachim
authors.initials: J
authors.lastname: Müller
authors.affiliation: Institute for Parasitology,Vetsuisse Faculty,University of Berne,Länggass-Strasse 122,CH-3012 Bern,Switzerland.
authors.forename: Vreni
authors.initials: V
authors.lastname: Balmer
authors.affiliation: Institute for Parasitology,Vetsuisse Faculty,University of Berne,Länggass-Strasse 122,CH-3012 Bern,Switzerland.
authors.forename: Vera
authors.initials: V
authors.lastname: Manser
authors.affiliation: CIISA,Faculdade de Medicina Veterinária,ULisboa,Avenida da Universidade Técnica,1300-477 Lisboa,Portugal.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Leitão
authors.affiliation: Institute for Parasitology,Vetsuisse Faculty,University of Berne,Länggass-Strasse 122,CH-3012 Bern,Switzerland.
authors.forename: Andrew
authors.initials: A
authors.lastname: Hemphill
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis / Q000097:blood; D000953:Antigens, Protozoan / Q000737:chemistry / Q000276:immunology*; D001921:Brain / Q000469:parasitology; D002522:Chlorocebus aethiops; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005260:Female; D007111:Immunity, Cellular; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D008024:Ligands; D051379:Mice; D008807:Mice, Inbred BALB C; D018688:Neospora / Q000276:immunology* / Q000378:metabolism; D010920:Placenta / Q000276:immunology / Q000469:parasitology; D011247:Pregnancy; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000276:immunology* / Q000378:metabolism; D014709:Vero Cells
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D016207:Cytokines; D007074:Immunoglobulin G; D008024:Ligands; D011993:Recombinant Fusion Proteins; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2
keywords: Neosporosis; chimeric antigen; innate and adaptive immune response; outer membrane lipoprotein I; toll-like receptor 2