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National Vaccine Program Office
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Proposal Number: | C23 |
PI Name: | Ball, Robert, MD, MPH, ScM |
PI Email: | |
PI Title: | Chief |
Project Title: | Arthritis after lyme vaccine: A case-control study of HLA type and T-cell reactivity to recombinant outer surface protein A and human leukocyte function-associated Antigen-1. |
Project Start: | 2002 |
Project End: | 2004 |
Abstract: The goal of this Vaccine Adverse Event Reporting System (VAERS)-based case-control study is to explore a possible association between development of arthritis following Lyme vaccination and the presence of Treatment Resistant Lyme Arthritis (TRLA)-associated Human Leukocyte Antigen (HLA)-DRB1 alleles and T-lymphocyte reactivity to the OspA protein and to human leukocyte function-associated antigen-1 (hLFA-1).
A small percentage of patients with Lyme disease infection, caused by the tickborne spirochete Borrelia burgdorferi, develop TRLA. TRLA has been associated with the presence of certain Class II (HLA) DRB1 alleles, including HLA-DRB1*0401. One proposed mechanism of TRLA is an autoimmune response to a human protein, hLFA-1, due to molecular mimicry between an epitope of the Bb Outer surface protein-A (OspA165-173) and an hLFA-1 epitope (hLFA1αL332-340). The TRLA HLA DRB1 alleles are proposed to be responsible for presenting these antigens to T-cells that play a role in TRLA.
The Lyme disease vaccine licensed in 1998 contains recombinant OspA (rOspA). Consequently, individuals who have the TRLA associated HLA-DRB1 alleles could, in theory, be at risk of developing an autoimmune arthritis, similar to TRLA, following Lyme vaccination.
We propose a VAERS-based case-control study to explore whether an association might possibly exist between arthritis following Lyme vaccination and the presence of the TRLA associated HLA-DRB1 alleles, and T-lymphocyte reactivity to both of the OspA and hLFA-1 epitopes. This study is relevant to the hypothesis that a subset of persons might be at risk of developing an autoimmune inflammatory arthritis after Lyme vaccine due to a genotype (HLA type) that is too rare to have been detected in the pre-licensure clinical trial.
Institution: Food and Drug Administration
Date: July 2003
Last revised: January 13, 2004
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