Laboratory Evaluation of B. burgdorferi Infection
in the Subject Who Has Received Lyme Vaccine

Philip J. Molloy, MD, FACP
Medical Director

Lyme disease is a multisystem inflammatory disease caused by infection with Borrelia burgdorferi. Although the diagnosis of Lyme disease is a clinical one, laboratory confirmation is available and often provides very useful information for the clinician. Excellent recent reviews on clinical and laboratory features of Lyme disease are available.(1),(2) Early diagnosis is very important. Treatment is usually effective.

In addition to focusing on accurate recognition and appropriate treatment, attempts to manage this infection have also focused attention on preventing Lyme disease. The prophylactic treatment of asymptomatic tick bites, pesticidal agents against the Ixodes tick vector, and control of infected deer populations have all been considered. More recently the development of vaccines against B. burgdorferi has been the object of more intense research efforts.

Early animal models used inactivated whole spirochetal organisms, and demonstrated protection against challenge with live B. burgdorferi in hamsters. Protection could be passively transferred by transfusing serum from immunized animals into non-immunized recipients, showing that this protection is antibody mediated. Concerns over using whole cell vaccine preparations, and the subsequent ability to isolate purified B. burgdorferi antigens by recombinant technology, led to the current evolution of Lyme vaccines using the spirochetal outer surface lipoprotein A (OspA), an abundant and highly immunogenic protein on the surface of pathogenic B. burgdorferi.

This led to the execution of two large scale, prospective, controlled human trials to evaluate the safety and efficacy of recombinant OspA vaccines in humans.(3),(4) Approximately 21,000 combined subjects were enrolled. The results have recently been published, demonstrating safety and efficacy.

When a vaccine is released for general use, it can be expected to be widely used in certain endemic areas, and this presents significant potential problems for laboratory testing for Lyme disease. Commonly used commercial ELISA tests will be positive in subjects vaccinated with OspA. Antibody Capture Enzyme Immunoassays, such as those performed at IMUGEN, are less likely to show positivity in vaccinated subjects, although low levels of antibody reactivity are not uncommonly seen (being present in approximately 20% of cases in our hands).

Furthermore on Western immunoblotting, for unexplained reasons, several reactive bands (weak to moderate) are observed, in addition to an intense OspA response at 30kd, when tested on native B. burgdorferi antigen preparations.(5)

This clearly complicates test interpretation and raises important issues of how to test for suspected Lyme disease in vaccine recipients.

A carefully performed and interpreted Lyme serologic profile can usually distinguish a patient infected with B. burgdorferi from a vaccinated patient. Important points to remember are:

1) Most commercial ELISA tests are positive in vaccinated patients.

2) This is less of a problem with antibody capture EIA although some reactivity may be observed (often below the cut-off for "positivity").

3) Conventional immunoblotting characteristically shows an intense OspA band at 30kd, as well as multiple other bands at other molecular weights.

A potential major advance and improvement in the laboratory testing for Lyme disease, should the vaccine be in widespread use, involves using a preparation of B. burgdorferi antigens lacking the OspA protein.

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