Lyme disease – treatment assessment based on anti-VIsE antibodies: a pilot study

Iwona Wojciechowska-Koszko, Paweł Kwiatkowski, Monika Sienkiewicz, Edward Kowalczyk, Barbara Dołęgowska


Introduction: Although the causative agent of Lyme disease (LD) has been known for a long time, and so far it has been possible to develop patterns useful in diagnosis and treatment, several factors continue to complicate the management of infection with Borrelia burgdorferi sensu lato. These include high species diversity of the spirochete causing LD and the lack of a treatment that could guarantee a complete and sustained eradication of infection in all patients. Therefore, the current study aimed to evaluate the effectiveness of treatment of patients with LD based on the measurement of LD-related antibodies generated in response to the highly immunogenic VlsE antigen evaluated using enzyme-linked immunosorbent assay (Lyme Trace ELISA).

Materials and methods: The study group consisted of 10 healthy volunteers (control group) and 21 outpatients (experimental group) with LD, living in the West Pomeranian Province of Poland. The serum samples of the experimental and control groups were tested with the anti-Borrelia IgG plus VlsE ELISA, anti-Borrelia IgG immunoblot, and anti-VlsE IgG Lyme Trace ELISA.

Results: Research showed that the mean value of anti-VIsE IgG antibody concentration decreased after treatment by 41.6%, 35.9%, and 31.7% in the serum dilutions 1:101, 1:1010, and 1:10100, respectively. A statistically significant difference was obtained in antibody concentration in the serum dilution 1:101 before (R) and after (R*) treatment. The R/R* ratio presented at least a 4-fold decrease in antibody concentration in 2 patients (9.5%), thereby suggesting the effectiveness of the therapy. In serum samples diluted at 1:101 and 1:1010, antibody levels showed an increase after treatment in 7 patients (33.3%), and at a dilution of 1:10100, this increase was found in 6 patients (28.6%). The R/R* ratio differed significantly between the subgroups, where the antibody concentration increased after treatment and then decreased.

Conclusion: Summing up, it can be concluded that the Lyme Trace ELISA assay used in the study to assess the level of anti-VlsE IgG antibodies showed insufficient satisfactory results in the assessment of monitoring the effectiveness of treatment in patients with LD before and after the treatment. The assessment of the effectiveness of treatment should, as such, still be based on the evaluation of the clinical symptoms of the disease, treating the quantification of IgG antibodies with the use of recombinant VlsE antigens as an additional tool.


Lyme disease; treatment; healthcare; VIsE; antibodies

Full Text:



Stanek G, Wormser GP, Gray J, Strle F. Lyme borreliosis. Lancet 2012;379(9814):461-73.

Hubálek Z. Epidemiology of Lyme borreliosis. Curr Probl Dermatol 2009;37:31-50.

Schotthoefer AM, Frost HM. Ecology and epidemiology of Lyme borreliosis. Clin Lab Med 2015;35(4):723-43.

Eddens T, Kaplan DJ, Anderson AJM, Nowalk AJ, Campfield BT. Insights from the geographic spread of the Lyme disease epidemic. Clin Infect Dis 2019;68(3):426-34.

Stanek G, Strle F. Lyme borreliosis – from tick bite to diagnosis and treatment. FEMS Microbiol Rev 2018;42(3):233-58.

Schoen RT. Lyme disease: diagnosis and treatment. Curr Opin Rheumatol 2020;32(3):247-54.

Stanek G, Fingerle V, Hunfeld KP, Jaulhac B, Kaiser R, Krause A, et al. Lyme borreliosis: clinical case definitions for diagnosis and management in Europe. Clin Microbiol Infect 2011;17(1):69-79.

Brouqui P, Bacellar F, Baranton G, Birtles RJ, Bjoërsdorff A, Blanco JR, et al. Guidelines for the diagnosis of tick-borne bacterial diseases in Europe. Clin Microbiol Infect 2004;10(12):1108-32.

Rauer S, Kastenbauer S, Hofmann H, Fingerle V, Huppertz HI, Hunfeld KP, et al. Guidelines for diagnosis and treatment in neurology – Lyme neuroborreliosis. Ger Med Sci 2020;18:Doc03.

O’Connell S. Recommendations for diagnosis and treatment of Lyme borreliosis: guidelines and consensus papers from specialist societies and expert groups in Europe and North America. uk/adult/lymeborreliosis.pdf (2.02.2022).

Hansmann Y. Treatment and prevention of Lyme disease. Curr Probl Dermatol 2009;37:111-29.

Sapi E, Kaur N, Anyanwu S, Luecke DF, Datar A, Patel S, et al. Evaluation of in vitro antibiotic susceptibility of different morphological forms of Borrelia burgdorferi. Infect Drug Resist 2011;4:97-113.

Sharma B, Brown AV, Matluck NE, Hu LT, Lewis K. Borrelia burgdorferi, the causative agent of Lyme disease, forms drug-tolerant persister cells. Antimicrob Agents Chemother 2015;59(8):4616-24.

Lacout A, El Hajjam ME, Marcy PY, Perronne C. The persistent Lyme disease: “True chronic Lyme disease” rather than “Post-treatment Lyme disease syndrome”. J Glob Infect Dis 2018;10(3):170-1.

Rebman AW, Aucott JN. Post-treatment Lyme disease as a model for persistent symptoms in Lyme disease. Front Med 2020;7:57.

Klempner MS, Hu LT, Evans J, Schmid CH, Johnson GM, Trevino RP, et al. Two controlled trials of antibiotic treatment in patients with persistent symptoms and a history of Lyme disease. N Engl J Med 2001;345(2):85-92.

Hunfeld KP, Brade V. Antimicrobial susceptibility of Borrelia burgdorferi sensu lato: what we know, what we don’t know, and what we need to know. Wien Klin Wochenschr 2006;118(21-22):659-68.

Wilske B, Fingerle V, Schulte-Spechtel U. Microbiological and serological diagnosis of Lyme borreliosis. FEMS Immunol Med Microbiol 2007;49(1):13-21.

Krzemień PJ. Role of VIsE/C6 antigen as a marker for early Lyme borreliosis diagnosis and monitoring the efectivness of its treatment. Heal Probl Civiliz 2017;11(2):87-92.

Wormser GP, Schriefer M, Aguero-Rosenfeld ME, Levin A, Steere AC, Nadelman RB, et al. Single-tier testing with the C6 peptide ELISA kit compared with two-tier testing for Lyme disease. Diagn Microbiol Infect Dis 2013;75(1):9-15.

Jacek E, Tang KS, Komorowski L, Ajamian M, Probst C, Stevenson B, et al. Epitope-specific evolution of human B cell responses to Borrelia burgdorferi VlsE protein from early to late stages of Lyme disease. J Immunol 2016;196(3):1036-43.

Marques AR. Laboratory diagnosis of Lyme disease: advances and challenges. Infect Dis Clin North Am 2015;29(2):295-307.

Wojciechowska-Koszko I, Mączyńska I, Szych Z, Giedrys-Kalemba S. Serodiagnosis of borreliosis: indirect immunofluorescence assay, enzyme- -linked immunosorbent assay and immunoblotting. Arch Immunol Ther Exp (Warsz) 2011;59(1):69-77.

Lager M, Dessau RB, Wilhelmsson P, Nyman D, Jensen GF, Matussek A, et al. Serological diagnostics of Lyme borreliosis: comparison of assays in twelve clinical laboratories in Northern Europe. Eur J Clin Microbiol Infect Dis 2019;38(10):1933-45.

Wojciechowska-Koszko I, Mnichowska-Polanowska M, Kwiatkowski P, Roszkowska P, Sienkiewicz M, Dołęgowska B. Immunoreactivity of Polish Lyme disease patient sera to specific Borrelia antigens – part 1. Diagnostics (Basel) 2021;11(11):2157.

Peltomaa M, McHugh G, Steere AC. Persistence of the antibody response to the VlsE sixth invariant region (IR6) peptide of Borrelia burgdorferi after successful antibiotic treatment of Lyme disease. J Infect Dis 2003;187(8):1178-86.

Marangoni A, Sambri V, Accardo S, Cavrini F, Mondardini V, Moroni A, et al. A decrease in the immunoglobulin G antibody response against the VlsE protein of Borrelia burgdorferi sensu lato correlates with the resolution of clinical signs in antibiotic-treated patients with early Lyme disease. Clin Vaccine Immunol 2006;13(4):525-9.

Strobino B, Steinhagen K, Meyer W, Scheper T, Saschenbrecker S, Schlumberger W, et al. A community study of Borrelia burgdorferi antibodies among individuals with prior Lyme disease in endemic areas. Healthcare (Basel) 2018;6(2):69.

Hubálek Z, Halouzka J. Distribution of Borrelia burgdorferi sensu lato genomic groups in Europe, a review. Eur J Epidemiol 1997;13(8):951-7.

Estrada-Peña A, Cutler S, Potkonjak A, Vassier-Tussaut M, Van Bortel W, Zeller H, et al. An updated meta-analysis of the distribution and prevalence of Borrelia burgdorferi s.l. in ticks in Europe. Int J Health Geogr 2018;17(1):41.

Philipp MT, Bowers LC, Fawcett PT, Jacobs MB, Liang FT, Marques AR, et al. Antibody response to IR6, a conserved immunodominant region of the VlsE lipoprotein, wanes rapidly after antibiotic treatment of Borrelia burgdorferi infection in experimental animals and in humans. J Infect Dis 2001;184(7):870-8.

Philipp MT, Wormser GP, Marques AR, Bittker S, Martin DS, Nowakowski J, et al. A decline in C6 antibody titer occurs in successfully treated patients with culture-confirmed early localized or early disseminated Lyme borreliosis. Clin Diagn Lab Immunol 2005;12(9):1069-74.

Gonzalez-Quintela A, Alende R, Gude F, Campos J, Rey J, Meijide LM, et al. Serum levels of immunoglobulins (IgG, IgA, IgM) in a general adult population and their relationship with alcohol consumption, smoking and common metabolic abnormalities. Clin Exp Immunol 2008;151(1):42-50.

John TM, Taege AJ. Appropriate laboratory testing in Lyme disease. Cleve Clin J Med 2019;86(11):751-9.

Kersten A, Poitschek C, Rauch S, Aberer E. Effects of penicillin, ceftriaxone, and doxycycline on morphology of Borrelia burgdorferi. Antimicrob Agents Chemother 1995;39(5):1127-33.

Brorson Ø, Brorson SH, Scythes J, MacAllister J, Wier A, Margulis L. Destruction of spirochete Borrelia burgdorferi round-body propagules (RBs) by the antibiotic tigecycline. Proc Natl Acad Sci USA 2009;106(44):18656-61.

Feng J, Auwaerter PG, Zhang Y. Drug combinations against Borrelia burgdorferi persisters in vitro: eradication achieved by using daptomycin, cefoperazone and doxycycline. PLoS One 2015;10(3):e0117207.


Copyright (c) 2022 Iwona Wojciechowska-Koszko, Paweł Kwiatkowski, Monika Sienkiewicz, Edward Kowalczyk, Barbara Dołęgowska

License URL: