An effective second-generation outer surface protein A-derived Lyme vaccine that eliminates a potentially autoreactive T cell epitope

doi:10.1073/pnas.0305680101

An effective second-generation outer surface protein A-derived Lyme vaccine that eliminates a potentially autoreactive T cell epitope

^†Department of Pathology, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111; and ^‡Center for Extracellular Matrix Biology, Albert B. Alkek Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, TX 77030

Edited by Harvey Cantor, Harvard Medical School, Boston, MA, and approved December 1, 2003 (received for review September 5, 2003)

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 1α_L chain (LFA-1α_L) in these patients. We generated a form of rOspA, FTK-OspA, in which the LFA-1α_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.

Footnotes

↵ § To whom correspondence should be addressed at: Department of Pathology, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111. E-mail: brigitte.huber{at}tufts.edu.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations: Bb, Borrelia burgdorferi; EV-Ctrl, empty vector lysate control; TRLA, treatment-resistant Lyme arthritis; OspA, outer surface protein A; rOspA, recombinant OspA; FTK-OspA, recombinant modified OspA; LFA-1α_L, leukocyte function-associated antigen 1α, L chain; hLFA, human LFA; THy, T cell hybridoma; APC, antigen-presenting cell.