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Adjuvanted Lyme Disease Vaccine

A Review of its Use in the Management of Lyme Disease

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Summary

Abstract

Lyme disease is a potentially serious infection which is caused by the spirochaete Borrelia burgdorferi and is endemic in certain areas of North America, Europe and Asia. Lyme disease vaccine (LYMErix™)1 is an adjuvanted formulation of the outer surface protein A (OspA) of the causative spirochaete. It acts by inducing high titres of anti-OspA antibodies (anti-OspA), which must be present in vaccinated individuals before exposure to B. burgdorferi to provide protection against Lyme disease.

Lyme disease vaccine efficacy against Lyme disease was 80% for definite and asymptomatic cases and 76% for definite cases at year 2 using the recommended dosage regimen [30µg at months 0,1 and 12 (0,1,12 schedule)] in a randomised, double-blind, multicentre trial in 10 936 enrolled adult volunteers who resided in areas of the US endemic for Lyme disease. On the basis of an anti-OspA correlate of protection, Lyme disease vaccine 30µg was equally effective when administered by a shorter schedule (0, 1, 6 schedule); ≥90% of adult volunteers developed protective anti-OspA titres with this or the 0,1,12 schedule. Although published data are fewer, a 0, 1,2 schedule has also shown promise in adults. In addition, virtually all children (aged 2 to 15 years) given Lyme disease vaccine 30µg developed protective anti-OspA titres, but published data are also limited and results of a large paediatric trial are awaited with interest.

Long term protection against Lyme disease appears to be possible with Lyme disease vaccine. Although anti-OspA titres decline rapidly after completion of the recommended schedule, booster doses of 30µg of the vaccine induced protective anti-OspA titres in ≥96% of adult volunteers when administered 12 and/or 24 months later.

Lyme disease vaccine 30µg is well tolerated: most vaccination-related adverse events were transient and mild or moderate in severity in clinical trials. The most common spontaneously reported adverse event was pain at the injection site in 24% of vaccine recipients (vs 7.6% of the placebo group). The incidence of spontaneously reported, early nonspecific systemic adverse events was <4% but was higher with the vaccine than with placebo for some events (e.g. myalgias, fever and chills but not arthralgia). There appeared to be no association between the vaccine and the incidence of arthritis or any late systemic adverse events. The tolerability profile of Lyme disease vaccine did not appear to vary with the schedule of administration, nor to differ between adults and children.

Conclusions: Lyme disease vaccine, an adjuvanted formulation of OspA, protects most adults against Lyme disease when administered by the recommended 0, 1, 12 schedule before disease exposure, and is well tolerated. The optimal schedule(s) of administration, duration of protection against Lyme disease, long term tolerability in adults and potential role in children are not fully defined for this vaccine. Lyme disease vaccine is indicated in North America for active immunisation of adults at moderate to high risk of contracting Lyme disease.

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References

  1. Centers for Disease Control and Prevention. Lyme disease —United States, 1996. MMWR 1997; 46(23): 531–5

    Google Scholar 

  2. Recommendations for the use of Lyme disease vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 1999 Jun 4; 48 Suppl. RR-7: 1–26

    Google Scholar 

  3. Steere AC, Malawista SE, Snydman DR, et al. Lyme arthritis. An epidemic or oligoarticular arthritis in chidren and adults in three Connecticut communities. Arthritis Rheum 1977 Jan–Feb; 20(1): 7–17

    PubMed  CAS  Google Scholar 

  4. Wormser GP. Vaccination as a modality to prevent Lyme disease —a status report. Infect Dis Clin North Am 1999 Mar; 13: 135

    Article  PubMed  CAS  Google Scholar 

  5. Steere AC. Lyme disease. N Engl J Med 1989 Aug; 321(9): 586–96

    Article  PubMed  CAS  Google Scholar 

  6. Wormser GP. Treatment and prevention of Lyme disease, with emphasis on antimicrobial therapy for neuroborreliosis and vaccination. Semin Neurol 1997 Mar; 17: 45–52

    Article  PubMed  CAS  Google Scholar 

  7. Meek JL, Roberts CL, Smith Jr EV, et al. Underreporting of Lyme disease by Connecticut physicians, 1992. J Public Health Mgmt Practice 1996; 2: 61–5

    CAS  Google Scholar 

  8. Coyle BS, Strickland GT, Liang YY, et al. The public health impact of Lyme disease in Maryland. J Infect Dis 1996; 173: 1260–2

    Article  PubMed  CAS  Google Scholar 

  9. Gerber MA, Shapiro ED, Burke GS, et al. Lyme disease in children in Southeastern Connecticut. N Engl J Med 1996; 335(17): 1270–4

    Article  PubMed  CAS  Google Scholar 

  10. Magid D, Schwartz B, Craft J, et al. Prevention of Lyme disease after tick bites. N Engl J Med 1992 Aug 20; 327(8): 534–41

    Article  PubMed  CAS  Google Scholar 

  11. Sood SK, Salzman MB, Johnson BJB, et al. Duration of tick attachment as a predictor of the risk of Lyme disease in an area in which Lyme disease is endemic. J Infect Dis 1996; 175: 996–9

    Article  Google Scholar 

  12. Loewen PS, Marra CA, Marra F. Systematic review of the treatment of early Lyme disease. Drugs 1999 Feb; 57: 157–73

    Article  PubMed  CAS  Google Scholar 

  13. Dennis DT. Epidemiology. In: Coyle P, editor. Lyme disease. Mosby Year Book, 1993: 27-36

  14. Sigal LH. Management of Lyme arthritis. Compr Ther 1999 April; 25(4): 228–38

    Article  PubMed  CAS  Google Scholar 

  15. Wharton M, Chorba TL, Vogt RL, et al. Case definitions for public health surveillance. MMWR 1990 Oct 19; 39 (RR-13): 1–43

    PubMed  CAS  Google Scholar 

  16. Nadelman RB, Wormser GP. Lyme borreliosis. Lancet 1998 Aug 15; 352: 557–65

    Article  PubMed  CAS  Google Scholar 

  17. Ziska MH, Donta ST, Demarest FC. Physician preferences in the diagnosis and treatment of Lyme disease in the United States. Infection 1996; 24(2): 182–6

    Article  PubMed  CAS  Google Scholar 

  18. Wormser GP, Horowitz HW, Nowakowski J, et al. Positive Lyme disease serology in patients with clinical and laboratory evidence of human granulocytic ehrlichiosis. Am J Clin Pathol 1997; 107: 142–7

    PubMed  CAS  Google Scholar 

  19. Steere AC, Sikand VK, Meurice F, et al. Vaccination against Lyme disease with recombinant Borrelia burgdorferi outer-surface lipoprotein A with adjuvant. N Engl J Med 1998 Jul 23; 339: 209–15

    Article  PubMed  CAS  Google Scholar 

  20. Feder Jr HM, Gerber MA, Cartter ML, et al. Prospective assessment of Lyme disease in a school-aged population in Connecticut. J Infect Dis 1995 May; 171: 1371–4

    Article  PubMed  Google Scholar 

  21. Steere AC, Parenti DL, Krause DS. Immunization against Lyme disease. Reply [letter]. N Engl J Med 1998 Nov 26; 339: 1639

    Article  Google Scholar 

  22. SmithKline Beecham. LYMErix™ Lyme disease vaccine (recombinant OspA) prescribing information. SmithKline Beecham, 1998 Dec

  23. Fikrig E, Barthold SW, Kantor FS, et al. Protection of mice against the Lyme disease agent by immunizing with recombinant OspA. Science 1990 Oct 26; 250: 553–6

    Article  PubMed  CAS  Google Scholar 

  24. Lovrich SD, Callister SM, DuChateau BK, et al. Abilities of OspA proteins from different seroprotective groups of Borrelia burgdorferi to protect hamsters from infection. Infect Immun 1995 Jun; 63: 2113–9

    PubMed  CAS  Google Scholar 

  25. Chang Y-F, Appel MJ, Jacobson RH, et al. Recombinant OspA protects dogs against infection and disease caused by Borrelia burgdorferi. Infect Immun 1995 Sep; 63: 3543–9

    PubMed  CAS  Google Scholar 

  26. Philipp MT, Lobet Y, Bohm Jr RP, et al. The outer surface protein A (OspA) vaccine against Lyme disease: efficacy in the rhesus monkey. Vaccine 1997 Dec; 15: 1872–87

    Article  PubMed  CAS  Google Scholar 

  27. Erdile LF, Brandt M-A, Warakomski DJ, et al. Role of attached lipid in immunogenicity of Borrelia burgdorferi OspA. Infect Immun 1993 Jan; 61(1): 81–90

    PubMed  CAS  Google Scholar 

  28. Van Hoecke C, Comberbach M, De Grave D, et al. Evaluation of the safety, reactogenicity and immunogenicity of three recombinant outer surface protein (OspA) Lyme vaccines in healthy adults. Vaccine 1996 Dec; 14: 1620–6

    Article  PubMed  Google Scholar 

  29. Sigal LH, Zahradnik JM, Lavin P, et al. A vaccine consisting of recombinant Borrelia burgdorferi outer-surface protein A to preventLyme disease. N Engl JMed 1998 Jul 23; 339: 216–22

    Article  CAS  Google Scholar 

  30. Keller D, Koster FT, Marks DH, et al. Safety and immunogenicity of a recombinant outer surface protein A Lyme vaccine. JAMA 1994 Jun 8; 271: 1764–8

    Article  PubMed  CAS  Google Scholar 

  31. Fikrig E, Telford III SR, Barthold SW, et al. Elimination of Borrelia burgdorferi from vector ticks feeding on Osp-A-immunized mice. Proc Natl Acad Sci U S A 1992 Jun 15; 89: 5418–21

    Article  PubMed  CAS  Google Scholar 

  32. de Silva AM, Fikrig E. Arthropod-and host-specific gene expression by Borrelia burgdorferi. J Clin Invest 1997; 99(3): 377–9

    Article  PubMed  Google Scholar 

  33. Parenti DL, Schoen RT, Sennewald E, et al. Evaluation of reactogenicity and immunogenicity of booster doses of LYMErix, recombinant L-OspA vaccine against Lyme disease (LD). [Abstract and poster no. 231.] Presented at 39th Interscience Conference on Antimicrobial Agents and Chemotherapy: 1999 Sep 26–29; San Francisco (CA)

  34. Van Hoecke C, Lebacq E, Beran J, et al. Alternative vaccination schedules (0, 1, and 6 months versus 0, 1, and 12 months) for a recombinant OspA Lyme disease vaccine. Clin Infect Dis 1999 Jun; 28: 1260–4

    Article  PubMed  Google Scholar 

  35. Schoen RT, Meurice F, Brunet CM, et al. Safety and immunogenicity of an outer surface protein A vaccine in subjects with previous Lyme disease. J Infect Dis 1995 Nov; 172: 1324–9

    Article  PubMed  CAS  Google Scholar 

  36. Van Hoecke C, Fu D, De Grave D, et al. Clinical and immunological assessment of a candidate Lyme disease vaccine in healthy adults: antibody persistence and effect of a booster dose at month 12. Vaccine 1998 Oct; 16: 1688–92

    Article  PubMed  Google Scholar 

  37. Feder Jr HM, Beran J, Van Hoecke C, et al. Immunogenicity of a recombinant Borrelia burgdorferi outer surface protein A vaccine against Lyme disease in children. J Pediatr 1999; 135: 575–9

    Article  PubMed  CAS  Google Scholar 

  38. Beran J, Dieussaert I, Van Hoecke C. Reactogenicity and immunogenicity of LYMErix, the Lyme disease vaccine, in healthy children aged 2–5 years [abstract no. P219]. Eighth International Conference on Lyme borreliosis and other emerging tick-borne diseases; 1999 Jun 20–24; Munich: 60

  39. Parenti DL, Schoen RT, Sikand VK, et al. Evaluation of reactogenicity and immunogenicity of LYMErix, recombinant L-OspA vaccine against Lyme disease, administered on two different schedules [abstract]. Clin Infect Dis 1998 Oct; 27: 1053

    Google Scholar 

  40. Parenti DL, Gillet M, Seenewald E, etal. Correlate of protection for Lyme disease (LD) using LYMErix™, recombinant, adjuvanted Borrelia burgdorferi outer surface lipoprotein A (L-OspA) vaccine [abstract no 704]. Clin Infect Dis 1998 Oct; 27(3): 1053

    Google Scholar 

  41. Golde WT, Piesman J, Dolan MC, et al. Reactivity with a specific epitope of outer surface protein A predicts protection from infection with the Lyme disease spirochete, Borrelia burgdorferi. Infect Immun 1997 Mar; 65: 882–9

    PubMed  CAS  Google Scholar 

  42. Kurtenbach K, Dizij A, Voet P, et al. Vaccination of natural reservoir hosts with recombinant lipidated OspA induces a transmission-blocking immunity against Lyme disease spirochaetes associated with high levels of LA-2 equivalent antibodies. Vaccine 1997 Oct; 15: 1670–4

    Article  PubMed  CAS  Google Scholar 

  43. Anderson S, Hauck WW. A new procedure for testing equivalence in comparative bioavailability and other clinical trials. Commun Stat Theory Meth 1983; 12: 2663–92

    Article  Google Scholar 

  44. Schoen R, Parenti D, Gillet M, et al. Persistence of antibody levels after vaccination with the Lyme disease vaccine (Lymerix) [abstract no. 100830]. Presented at the 37th Annual Meeting of the Infectious Diseases Society of America: 1999 Nov 18–21, Philadelphia (PA)

  45. Meurice F, Parenti D, Fu D, et al. Specific issues in the design and implementation of an efficacy trial for a Lyme disease vaccine. Clin Infect Dis 1997 Jul; 25 Suppl. 1: S71–5

    Article  PubMed  Google Scholar 

  46. Recommendations for test performance and interpretation from the Second National Conference on Serologic Diagnosis of Lyme Disease. MMWR 1995; 44(31): 590–1

    Google Scholar 

  47. Berger BW, Johnson RC, Kodner C, et al. Cultivation of Borrelia burgdorferi from erythema migrans lesions and perilesional skin. J Clin Microbiol 1992; 30(2): 359–61

    PubMed  CAS  Google Scholar 

  48. Norton JJ, Dressier F, Rutledge BJ, et al. Detection of Borrelia burgdorferi DNA by polymerase chain reaction in synovial fluid from patients with Lyme arthritis. N Engl J Med 1994; 330(4): 229–34

    Article  Google Scholar 

  49. Norton JJ, Bloom BJ, Rutledge BJ, et al. Detection of Borrelia burgdorferi DNA by polymerase chain reaction in cerebrospinal fluid in Lyme neuroborreliosis. J Infect Dis 1996; 174: 623–7

    Article  Google Scholar 

  50. SmithKlineBeecham. Post hoc analysis of LYMErix [Lyme disease vaccine (recombinant OspA)] efficacy by age in subjects with definite Lyme disease. SmithKline Beecham. (Data on file)

  51. SmithKlineBeecham. Number of vaccinees who experienced the same adverse event aftertwo doses. Smith Kline Beecham. (Data on file)

  52. Steere AC, Schoen RT, Taylor E. The clinical evolution of Lyme arthritis. Ann Intern Med 1987 Nov; 107(5): 725–31

    PubMed  CAS  Google Scholar 

  53. Gross DM, Forsthuber T, Tary-Lehmann M, et al. Identification of LFA-1 as a candidate autoantigen in treatment-resistant Lyme arthritis. Science 1998 Jul 31; 281: 703–6

    Article  PubMed  CAS  Google Scholar 

  54. Chen J, Field JA, Glickstein L, et al. Association of antibiotic treatment-resistant Lyme arthritis with T cell responses to dominant epitopes of outer suface protein A of Borrelia burgdorferi. Arthritis Rheum 1999 Sep; 42(9): 1813–22

    Article  PubMed  CAS  Google Scholar 

  55. Lengl-Janssen B, Strauss AF, Steere AC, et al. The T helper cell response in Lyme arthritis: differential recognition of Borrelia burgdorferi outer surface protein A in patients with treatment-resistant or treatment-responsive Lyme arthritis. J Exp Med 1994 Dec 1; 180(6): 2069–78

    Article  PubMed  CAS  Google Scholar 

  56. Kalish RA, Leong JM, Steere AC. Association of treatment-resistant chronic Lyme arthritis with HLA-DR4 and antibody reactivity to OspA and OspB of Borrelia burgdorferi. Infect Immun 1993; 61(7): 2774–9

    PubMed  CAS  Google Scholar 

  57. Wormser GP. A vaccine against Lyme Disease? Ann Intern Med 1995 Oct; 123: 627–9

    CAS  Google Scholar 

  58. O’Connell S. Lyme borreliosis. Curr Opin Infect Dis 1997; 10(2): 91–5

    Article  Google Scholar 

  59. Sigal LH. Lyme arthritis: lessons learned and to be learned. Arthritis Rheum 1999 Sep; 42(9): 1809–12

    Article  PubMed  CAS  Google Scholar 

  60. SmithKline Beecham. Long term safety of LYMErix. 1999, Data on file

  61. Meltzer MI, Dennis DT, Orloski KA. The cost effectiveness of vaccinating against Lyme disease [downloaded from http://www.cdc.gove/nciod/eid/vol5no3/meltzer.htm on 29 Sep 1999]. Emerg Infect Dis 1999 May–Jun; 5 (3)

  62. CDC LYMErix recommendations to be published in next few weeks. FDC Pink 1999 Mar 1; 61: 23–4

    Google Scholar 

  63. Plotkin SA, Committee on Infectious Diseases 1990 to 1991. Treatment of Lyme borreliosis. Pediatrics 1991 Jul; 88: 176–9

    Google Scholar 

  64. Cimmino MA, Moggiana GL, Parisi M, et al. Treatment of lyme arthritis. Infection 1996 Jan–Feb; 24: 91–4

    Article  PubMed  CAS  Google Scholar 

  65. Coyle PK, Luft BJ. Management of Lyme disease. Curr Opin Infect Dis 1995 Dec; 8: 444–9

    Article  Google Scholar 

  66. Hayes EB, Maupin GO, Mount GA, et al. Assessing the prevention effectiveness of local Lyme disease control. J Public Health Mgmt Practice 1999; 5(3): 84–92

    CAS  Google Scholar 

  67. Ma J, Bulger PA, Dante S, et al. Characterization of canine humoral immune responses to outer surface protein subunit vaccines and to natural infection by Lyme disease spiro-chetes. J Infect Dis 1995 Apr; 171: 909–15

    Article  PubMed  CAS  Google Scholar 

  68. Straubinger RK, Chang YF, Jacobson RH, et al. Sera from OspA-vaccinated dogs, but not those from tick-infected dogs, inhibit in vitro growth of Borrelia burgdorferi. J Clin Microbiol 1995 Oct; 33: 2745–51

    PubMed  CAS  Google Scholar 

  69. SB LYMErix compliance system is registering 100 physicians per day. Pharm Approv Mon 1999 Feb; 4: 3–4

    Google Scholar 

  70. Van Hoecke C, Voet P, De Grave D, et al. Immunogenicity of A1(OH)3-adsorbed and plain lipoprotein OspA vaccine formulations in monkeys and man. 34th Int Conf Antimicro Ag Chemother 1994: 25

  71. Aguero-Rosenfeld ME, Roberge J, Carbonaro CA, et al. Effects of OspA vaccination on Lyme disease serologic testing. J Clin Microbiol 1999; 37(11): 3718–21

    PubMed  CAS  Google Scholar 

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  1. Adis International Limited, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, Auckland 10, New Zealand

    Susan V. Onrust & Karen L. Goa

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  1. Susan V. Onrust
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Correspondence to Karen L. Goa.

Additional information

Various sections of the manuscript reviewed by: J. Beran, Purkyne Military Medical Academy, Hradec Kralové, Czech Republic; F. Marra, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver Hospital and Health Sciences Centre, Vancouver, British Columbia, Canada; G. Nichol, Department of Medicine, Ottawa General Hospital, Ottawa, Ontario, Canada; L.H. Sigal, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, New Brunswick, New York, USA; A.-M. Svennerholm, Department of Medical Microbiology and Immunology, Göteborg University, Göteborg, Sweden; S.R. Telford, Harvard School of Public Health, Department of Immunology and Infectious Diseases, Boston, Massachusetts, USA; G. Wormser, Division of Infectious Disease, Lyme Disease Diagnostic Center, Westchester County Medical Center, New York Medical College, Valhalla, New York, USA.

Data Selection

Sources: Medical literature published in any language since 1966 on Lyme disease vaccine, identified using AdisBase (a proprietary database of Adis International, Auckland, New Zealand), Medline and EMBASE. Additional references were identified from the reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from the company developing the drug.

Search strategy: AdisBase search terms were ‘Lyme-disease-vaccine-smithkline-beecham’ or ‘Lyme-disease-vaccine’. Medline search terms were ‘Lyme-disease / prevention-and-control’ and ‘bacterial-vaccines’. EMBASE search terms were ‘Lyme-disease’ and ‘bacterialvaccine’. Searches were last updated 11 Jan 2000.

Selection: Studies in volunteers who received Lyme disease vaccine. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic data are also included.

Index terms: Lyme disease vaccine, LYMErix™, Lyme disease, Lyme borreliosis, B. burgdorferi, pharmacodynamics, therapeutic use, adverse events

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Onrust, S.V., Goa, K.L. Adjuvanted Lyme Disease Vaccine. Drugs 59, 281–299 (2000). https://doi.org/10.2165/00003495-200059020-00019

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