Abstract
Recombinant Lyme disease vaccines based on purified preparations of outer surface protein A (OspA) have been shown to be effective in preventing transmission of Borrelia burgdorferi in experimental animal models and are now being tested in humans. Since the most widely used screening tests for Lyme disease are based on a whole-cell sonicate of B. burgdorferi, serologic false positivity in vaccinated persons could result from reactivity to OspA within the antigen preparation. In order to avoid serologic false positivity in vaccinated subjects, we developed an immunoassay based on a low-passage-number, naturally occurring variant of B. burgdorferi which lacks the plasmid encoding OspA and OspB. The use of an antigen preparation derived from this organism provided sensitive and specific detection of B. burgdorferi seropositivity in experimental animals and in human Lyme disease cases. The OspA-B-negative enzyme-linked immunosorbent assay (ELISA) also appeared to be capable of discriminating the vaccinated state from vaccine failure and natural infection in experimental animals. Sera from human subjects participating in a vaccine trial gave false-positive results with an ELISA based on an OspA-containing strain, but no such reactivity was observed when the OspA-negative ELISA was used. We conclude that low-passage-number OspA-B-negative isolates in immunoassays may become useful for the immunologic discrimination of the vaccinated state, natural infection, and vaccine failure.
Full Text
The Full Text of this article is available as a PDF (300.1 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Anderson J. F., Flavell R. A., Magnarelli L. A., Barthold S. W., Kantor F. S., Wallich R., Persing D. H., Mathiesen D., Fikrig E. Novel Borrelia burgdorferi isolates from Ixodes scapularis and Ixodes dentatus ticks feeding on humans. J Clin Microbiol. 1996 Mar;34(3):524–529. doi: 10.1128/jcm.34.3.524-529.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bakken J. S., Dumler J. S., Chen S. M., Eckman M. R., Van Etta L. L., Walker D. H. Human granulocytic ehrlichiosis in the upper Midwest United States. A new species emerging? JAMA. 1994 Jul 20;272(3):212–218. [PubMed] [Google Scholar]
- Barbour A. G. Isolation and cultivation of Lyme disease spirochetes. Yale J Biol Med. 1984 Jul-Aug;57(4):521–525. [PMC free article] [PubMed] [Google Scholar]
- Barthold S. W., Fikrig E., Bockenstedt L. K., Persing D. H. Circumvention of outer surface protein A immunity by host-adapted Borrelia burgdorferi. Infect Immun. 1995 Jun;63(6):2255–2261. doi: 10.1128/iai.63.6.2255-2261.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Benach J. L., Bosler E. M., Hanrahan J. P., Coleman J. L., Habicht G. S., Bast T. F., Cameron D. J., Ziegler J. L., Barbour A. G., Burgdorfer W. Spirochetes isolated from the blood of two patients with Lyme disease. N Engl J Med. 1983 Mar 31;308(13):740–742. doi: 10.1056/NEJM198303313081302. [DOI] [PubMed] [Google Scholar]
- Burgdorfer W., Barbour A. G., Hayes S. F., Benach J. L., Grunwaldt E., Davis J. P. Lyme disease-a tick-borne spirochetosis? Science. 1982 Jun 18;216(4552):1317–1319. doi: 10.1126/science.7043737. [DOI] [PubMed] [Google Scholar]
- Craven R. B., Quan T. J., Bailey R. E., Dattwyler R., Ryan R. W., Sigal L. H., Steere A. C., Sullivan B., Johnson B. J., Dennis D. T. Improved serodiagnostic testing for Lyme disease: results of a multicenter serologic evaluation. Emerg Infect Dis. 1996 Apr-Jun;2(2):136–140. doi: 10.3201/eid0202.960211. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dressler F., Whalen J. A., Reinhardt B. N., Steere A. C. Western blotting in the serodiagnosis of Lyme disease. J Infect Dis. 1993 Feb;167(2):392–400. doi: 10.1093/infdis/167.2.392. [DOI] [PubMed] [Google Scholar]
- Dumler J. S., Bakken J. S. Ehrlichial diseases of humans: emerging tick-borne infections. Clin Infect Dis. 1995 May;20(5):1102–1110. doi: 10.1093/clinids/20.5.1102. [DOI] [PubMed] [Google Scholar]
- Engstrom S. M., Shoop E., Johnson R. C. Immunoblot interpretation criteria for serodiagnosis of early Lyme disease. J Clin Microbiol. 1995 Feb;33(2):419–427. doi: 10.1128/jcm.33.2.419-427.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fikrig E., Barthold S. W., Kantor F. S., Flavell R. A. Long-term protection of mice from Lyme disease by vaccination with OspA. Infect Immun. 1992 Mar;60(3):773–777. doi: 10.1128/iai.60.3.773-777.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fikrig E., Barthold S. W., Kantor F. S., Flavell R. A. Protection of mice against the Lyme disease agent by immunizing with recombinant OspA. Science. 1990 Oct 26;250(4980):553–556. doi: 10.1126/science.2237407. [DOI] [PubMed] [Google Scholar]
- Fikrig E., Huguenel E. D., Berland R., Rahn D. W., Hardin J. A., Flavell R. A. Serologic diagnosis of Lyme disease using recombinant outer surface proteins A and B and flagellin. J Infect Dis. 1992 Jun;165(6):1127–1132. doi: 10.1093/infdis/165.6.1127. [DOI] [PubMed] [Google Scholar]
- Fikrig E., Telford S. R., 3rd, Barthold S. W., Kantor F. S., Spielman A., Flavell R. A. Elimination of Borrelia burgdorferi from vector ticks feeding on OspA-immunized mice. Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5418–5421. doi: 10.1073/pnas.89.12.5418. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gerber M. A., Shapiro E. D., Bell G. L., Sampieri A., Padula S. J. Recombinant outer surface protein C ELISA for the diagnosis of early Lyme disease. J Infect Dis. 1995 Mar;171(3):724–727. doi: 10.1093/infdis/171.3.724. [DOI] [PubMed] [Google Scholar]
- Kolbert C. P., Podzorski D. S., Mathiesen D. A., Wortman A. T., Gazumyan A., Schwartz I., Persing D. H. Two geographically distinct isolates of Borrelia burgdorferi from the United States share a common unique ancestor. Res Microbiol. 1995 Jun;146(5):415–424. doi: 10.1016/0923-2508(96)80287-7. [DOI] [PubMed] [Google Scholar]
- Krause P. J., Telford S. R., 3rd, Spielman A., Sikand V., Ryan R., Christianson D., Burke G., Brassard P., Pollack R., Peck J. Concurrent Lyme disease and babesiosis. Evidence for increased severity and duration of illness. JAMA. 1996 Jun 5;275(21):1657–1660. [PubMed] [Google Scholar]
- Mertz L. E., Wobig G. H., Duffy J., Katzmann J. A. Ticks, spirochetes, and new diagnostic tests for Lyme disease. Mayo Clin Proc. 1985 Jun;60(6):402–406. doi: 10.1016/s0025-6196(12)60851-9. [DOI] [PubMed] [Google Scholar]
- Persing D. H., Herwaldt B. L., Glaser C., Lane R. S., Thomford J. W., Mathiesen D., Krause P. J., Phillip D. F., Conrad P. A. Infection with a babesia-like organism in northern California. N Engl J Med. 1995 Feb 2;332(5):298–303. doi: 10.1056/NEJM199502023320504. [DOI] [PubMed] [Google Scholar]
- Schwan T. G., Piesman J., Golde W. T., Dolan M. C., Rosa P. A. Induction of an outer surface protein on Borrelia burgdorferi during tick feeding. Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2909–2913. doi: 10.1073/pnas.92.7.2909. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Steere A. C., Grodzicki R. L., Kornblatt A. N., Craft J. E., Barbour A. G., Burgdorfer W., Schmid G. P., Johnson E., Malawista S. E. The spirochetal etiology of Lyme disease. N Engl J Med. 1983 Mar 31;308(13):733–740. doi: 10.1056/NEJM198303313081301. [DOI] [PubMed] [Google Scholar]
- Steere A. C. Lyme disease: a growing threat to urban populations. Proc Natl Acad Sci U S A. 1994 Mar 29;91(7):2378–2383. doi: 10.1073/pnas.91.7.2378. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Steere A. C., Malawista S. E., Snydman D. R., Shope R. E., Andiman W. A., Ross M. R., Steele F. M. Lyme arthritis: an epidemic of oligoarticular arthritis in children and adults in three connecticut communities. Arthritis Rheum. 1977 Jan-Feb;20(1):7–17. doi: 10.1002/art.1780200102. [DOI] [PubMed] [Google Scholar]
- Wormser G. P., Horowitz H. W., Dumler J. S., Schwartz I., Aguero-Rosenfeld M. False-positive Lyme disease serology in human granulocytic ehrlichiosis. Lancet. 1996 Apr 6;347(9006):981–982. doi: 10.1016/s0140-6736(96)91475-0. [DOI] [PubMed] [Google Scholar]