title: Tripalmitoyl-S-glyceryl-cysteine-dependent OspA vaccination of toll-like receptor 2-deficient mice results in effective protection from Borrelia burgdorferi challenge.
abstract: Toll-like receptor 2 (TLR2) is a transmembrane signal transducer for tripalmitoyl-S-glyceryl-cysteine (Pam(3)Cys)-modified lipoproteins, including OspA from the Lyme disease spirochete Borrelia burgdorferi. The Pam(3)Cys modification provides adjuvant activity for inducing humoral responses, suggesting that TLR2 could function as the adjuvant receptor for the OspA vaccine. The importance of TLR2 in the humoral response to OspA was confirmed, because overall levels of immunoglobulin G (IgG) were reduced in TLR2-deficient mice, when compared with those in wild-type mice. However, the levels of production of IgG1 were similar in both mouse strains, and the levels of induction of protective immunity were comparable. Unlipidated OspA was not immunogenic in wild-type or TLR2-deficient mice, indicating the lipid modification was active in the absence of TLR2. These findings indicate that the Pam(3)Cys modification of bacterial lipoprotein has adjuvant properties independent of TLR2 signaling.
authors.affiliation: Department of Pathology, University of Utah, Salt Lake City, Utah 84132, USA.
authors.forename: Alyson
authors.initials: A
authors.lastname: Yoder
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Ma
authors.forename: Mario T
authors.initials: MT
authors.lastname: Philipp
authors.forename: Marta
authors.initials: M
authors.lastname: Heilbrun
authors.forename: John H
authors.initials: JH
authors.lastname: Weis
authors.forename: Carsten J
authors.initials: CJ
authors.lastname: Kirschning
authors.forename: R Mark
authors.initials: RM
authors.lastname: Wooten
authors.forename: Janis J
authors.initials: JJ
authors.lastname: Weis
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000954:Antigens, Surface / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D001428:Bacterial Vaccines / Q000276:immunology*; D003545:Cysteine / Q000031:analogs & derivatives* / Q000502:physiology*; D008074:Lipoproteins; D008193:Lyme Disease / Q000517:prevention & control*; D008562:Membrane Glycoproteins / Q000172:deficiency* / Q000502:physiology; D051379:Mice; D008809:Mice, Inbred C3H; D011956:Receptors, Cell Surface / Q000172:deficiency* / Q000502:physiology; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D014611:Vaccination
chemical_list: D000907:Antibodies, Bacterial; D000954:Antigens, Surface; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D008074:Lipoproteins; D008562:Membrane Glycoproteins; C072045:OspA protein; D011956:Receptors, Cell Surface; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; C038837:tripalmitoyl cysteine; D003545:Cysteine