title: Anchoring tick salivary anti-complement proteins IRAC I and IRAC II to membrane increases their immunogenicity.
abstract: Tick salivary proteins are promising targets for the development of anti-tick vaccines. Recently, we described two paralogous anti-complement proteins, called Ixodes ricinus anti-complement (IRAC) proteins I and II, that are co-expressed in tick I. ricinus salivary glands. However, our previous attempts to immunize rabbits against IRAC via infection with recombinant Bovine herpesvirus 4 (BoHV-4) vectors invariably failed although both recombinants expressed high levels of functional IRAC proteins in vitro. As IRAC are soluble monovalent antigens, one of the possible explanations is that monovalent ligation of the B-cell receptor induces receptor activation but fails to promote antigen presentation, a phenomenon that is thought to induce a state of B-cell tolerance. In the present study, we tried to increase IRAC immunogenicity by expressing them as oligovalent antigens. To this end, IRAC were fused to membrane anchors and BoHV-4 vectors expressing these recombinant forms were produced. The immunization potentials of recombinant viruses expressing either secreted or transmembrane IRAC proteins were then compared. While the former did not induce a detectable immune response against IRAC, the latter led to high titres of anti-IRAC antibodies that only marginally affected tick blood feeding. All together, the data presented in this study demonstrate that the immunogenicity of a soluble antigen can be greatly improved by anchoring it in membrane.
authors.affiliation: Immunology-Vaccinology (B43b), Department of Infectious and Parasitic Diseases (B43b), Faculty of Veterinary Medicine, University of Liège, B-4000 Liège, Belgium.
authors.forename: Laurent
authors.initials: L
authors.lastname: Gillet
authors.forename: Hélène
authors.initials: H
authors.lastname: Schroeder
authors.forename: Jan
authors.initials: J
authors.lastname: Mast
authors.forename: Muriel
authors.initials: M
authors.lastname: Thirion
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Renauld
authors.forename: Benjamin
authors.initials: B
authors.lastname: Dewals
authors.forename: Alain
authors.initials: A
authors.lastname: Vanderplasschen
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D002415:Cats; D002417:Cattle; D002448:Cell Adhesion; D002460:Cell Line; D003169:Complement Inactivator Proteins / Q000276:immunology*; D003165:Complement System Proteins / Q000378:metabolism; D004285:Dogs; D005786:Gene Expression Regulation; D018884:Ixodes / Q000378:metabolism*; D011817:Rabbits; D012463:Saliva / Q000737:chemistry*
chemical_list: D000911:Antibodies, Monoclonal; D003169:Complement Inactivator Proteins; D003165:Complement System Proteins