Correspondence

Detection of Lyme Disease after OspA Vaccine

N Engl J Med 1997; 337:794-795September 11, 1997

Article

To the Editor:

The diagnosis of a new Lyme disease infection by conventional assays may be difficult in persons who have antibodies to or immunologic memory of Borrelia burgdorferi proteins. This was the case in a recipient of vaccine containing recombinant outer-surface protein A (OspA) of B. burgdorferi (Connaught).1 Analysis of the antibody and antigen constituents of B. burgdorferi–specific immune complexes can distinguish between past and active infection in such patients.2,3

Several years before vaccination, a woman with Lyme disease documented by the presence of erythema migrans and by a positive polymerase-chain-reaction assay of a skin-biopsy specimen was successfully treated with intravenous antibiotics. On March 21, 1994, she entered a vaccine trial and received the vaccine containing OspA. On May 19, 1994, an engorged deer tick was found on the patient; it had probably been present for three days. A few days later, she reported a stiff neck and was unable to touch her chin to her chest; she also had mild headache, as well as generalized aches, myalgias, and posterior cervical lymphadenopathy, but no erythema migrans. On June 1, when a blood sample was drawn at the trial center, symptoms had abated except for lymphadenopathy. Between June 7 and June 10, such profound fatigue developed that she could not stay awake past noon, and she had a slight headache. On June 10, the trial center prescribed oral antibiotics for Lyme disease, based on a change in the results of immunoblotting. By early August, the patient's symptoms had resolved.

We independently analyzed serum obtained during the symptomatic period. We detected B. burgdorferi–specific immune complexes containing antibody to unique proteins, including recombinant OspA, and the corresponding antigen.2 This finding alone is highly suggestive of an active infection. Immune-complex antibody reactivity was also found on immunoblot testing in the region of outer-surface proteins B and C (OspB and OspC). The relevance of this finding is further supported by the absence of such findings just before vaccination and by the decreased intensity of blot bands and the marked decrease in optical-density readings on an enzyme-linked immunosorbent assay run at the same time, near the end of the patient's antibiotic therapy (Figure 1Figure 1Immunoreactivity of the Patient to Recombinant Borrelia burgdorferi Outer-Surface Protein A (OspA) in Western Blot Analyses with Biotin and Avidin.).

Physicians may eventually be faced with possible vaccine failures, and the presentation of Lyme disease may be modified in patients who are infected after vaccination. Partial protection gained from the OspA vaccine may be associated with the absence of erythema migrans, which would mask the infection at its earliest, most treatable stage.4 Not all vaccine-induced OspA antibodies are capable of killing the organism.5 Regardless of the reasons for the failure of the vaccine in the patient we studied, clinicians should recognize that not every vaccine recipient will be protected and should be aware of the difficulty of diagnosing B. burgdorferi infection in previously exposed or vaccinated subjects. As this case illustrates, however, there is a practical laboratory method to detect infection in such persons.

Steven E. Schutzer, M.D.
Jennifer Luan, M.D.
University of Medicine and Dentistry of New Jersey, Newark, NJ 07103

P.K. Coyle, M.D.
State University of New York at Stony Brook, Stony Brook, NY 11794

5 References

1
Keller D, Koster FT, Marks DH, Hosbach P, Erdile LF, Mays JP. Safety and immunogenicity of a recombinant outer surface protein A Lyme vaccine. JAMA 1994;271:1764-1768
CrossRef | Web of Science | Medline

2
Schutzer SE, Coyle PK, Dunn JJ, Luft BJ, Brunner M. Early and specific antibody response to OspA in Lyme disease. J Clin Invest 1994;94:454-457
CrossRef | Web of Science | Medline

3
Schutzer SE, Coyle PK, Belman AL, Golightly MG, Drulle J. Sequestration of antibody to Borrelia burgdorferi in immune complexes in seronegative Lyme disease. Lancet 1990;335:312-315
CrossRef | Web of Science | Medline

4
Foley DM, Wang Y-P, Wu X-Y, Blanco DR, Lovett MA, Miller JN. Acquired resistance to Borrelia burgdorferi infection in the rabbit: comparison between outer surface protein A vaccine and infection-derived immunity. J Clin Invest 1997;99:2030-2035
CrossRef | Web of Science | Medline

5
Padilla ML, Callister SM, Schell RF, et al. Characterization of the protective borreliacidal antibody response in humans and hamsters after vaccination with a Borrelia burgdorferi outer surface protein A vaccine. J Infect Dis 1996;174:739-746
CrossRef | Web of Science | Medline

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