title: An effective second-generation outer surface protein A-derived Lyme vaccine that eliminates a potentially autoreactive T cell epitope.
abstract: The antigenic component of a common Lyme disease vaccine is recombinant outer surface protein A (rOspA) of Borrelia burgdorferi (Bb), the causative agent of Lyme disease. Coincidentally, patients with chronic, treatment-resistant Lyme arthritis develop an immune response against OspA, whereas those with acute Lyme disease usually do not. Treatment-resistant Lyme arthritis occurs in a subset of Lyme arthritis patients and is linked to HLA.DRB1*0401 (DR4) and related alleles. Recent work from our laboratory identified T cell crossreactivity between epitopes of OspA and lymphocyte function-associated antigen 1alpha(L) chain (LFA-1alpha(L)) in these patients. We generated a form of rOspA, FTK-OspA, in which the LFA-1alpha(L)/rOspA crossreactive T cell epitope was mutated to reduce the possible risk of autoimmunity in genetically susceptible individuals. FTK-OspA did not stimulate human or mouse DR4-restricted, WT-OspA-specific T cells, whereas it did stimulate antibody responses specific for WT-OspA that were similar to mice vaccinated WT-OspA. We show here that the protective efficacy of FTK-OspA is indistinguishable from that of WT-OspA in vaccination trials, as both C3H/HeJ and BALB/c FTK-OspA-vaccinated mice were protected from Bb infection. These data demonstrate that this rOspA-derived vaccine lacking the predicted cross-reactive T cell epitope, but retaining the capacity to elicit antibodies against infection, is effective in generating protective immunity.
authors.affiliation: Department of Pathology, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111, USA.
authors.forename: Theresa A
authors.initials: TA
authors.lastname: Willett
authors.forename: Abbie L
authors.initials: AL
authors.lastname: Meyer
authors.forename: Eric L
authors.initials: EL
authors.lastname: Brown
authors.forename: Brigitte T
authors.initials: BT
authors.lastname: Huber
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000276:immunology*; D015551:Autoimmunity; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D001428:Bacterial Vaccines; D018984:Epitopes, T-Lymphocyte; D005260:Female; D008074:Lipoproteins; D008193:Lyme Disease / Q000517:prevention & control; D022123:Lyme Disease Vaccines / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D010446:Peptide Fragments / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology*
chemical_list: D000954:Antigens, Surface; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D018984:Epitopes, T-Lymphocyte; D008074:Lipoproteins; D022123:Lyme Disease Vaccines; C072045:OspA protein; D010446:Peptide Fragments; D014614:Vaccines, Synthetic