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An effective second-generation outer surface protein A-derived Lyme vaccine that eliminates a potentially autoreactive T cell epitope.
Proc Natl Acad Sci U S A. 2004 Feb 03; 101(5):1303-8.PN

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+Show Affiliations

Department of Pathology, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

14742868

Citation

Willett, Theresa A., et al. "An Effective Second-generation Outer Surface Protein A-derived Lyme Vaccine That Eliminates a Potentially Autoreactive T Cell Epitope." Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 5, 2004, pp. 1303-8.
Willett TA, Meyer AL, Brown EL, et al. An effective second-generation outer surface protein A-derived Lyme vaccine that eliminates a potentially autoreactive T cell epitope. Proc Natl Acad Sci USA. 2004;101(5):1303-8.
Willett, T. A., Meyer, A. L., Brown, E. L., & Huber, B. T. (2004). An effective second-generation outer surface protein A-derived Lyme vaccine that eliminates a potentially autoreactive T cell epitope. Proceedings of the National Academy of Sciences of the United States of America, 101(5), 1303-8.
Willett TA, et al. An Effective Second-generation Outer Surface Protein A-derived Lyme Vaccine That Eliminates a Potentially Autoreactive T Cell Epitope. Proc Natl Acad Sci USA. 2004 Feb 3;101(5):1303-8. PubMed PMID: 14742868.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - An effective second-generation outer surface protein A-derived Lyme vaccine that eliminates a potentially autoreactive T cell epitope. AU - Willett,Theresa A, AU - Meyer,Abbie L, AU - Brown,Eric L, AU - Huber,Brigitte T, Y1 - 2004/01/23/ PY - 2004/1/27/pubmed PY - 2004/3/10/medline PY - 2004/1/27/entrez SP - 1303 EP - 8 JF - Proceedings of the National Academy of Sciences of the United States of America JO - Proc. Natl. Acad. Sci. U.S.A. VL - 101 IS - 5 N2 - 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. SN - 0027-8424 UR - https://www.unboundmedicine.com/medline/citation/14742868/An_effective_second_generation_outer_surface_protein_A_derived_Lyme_vaccine_that_eliminates_a_potentially_autoreactive_T_cell_epitope_ L2 - http://www.pnas.org/cgi/pmidlookup?view=long&pmid=14742868 DB - PRIME DP - Unbound Medicine ER -