Animal and human antibodies reactive with the outer surface protein A and B of Borrelia burgdorferi are borreliacidal, in vitro, in the presence of complement

Sambri, Vittorio

doi:10.1016/0928-8244(93)90045-6

Cited by 15 publications

(27 citation statements)

References 19 publications

(22 reference statements)

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“…In addition, assays of several sera that tested positive by WB and negative by BAT appeared to have yielded false positives. Some sera did not contain borreliacidal antibodies, despite WB-detectable reactivities against multiple speciesspecific B. burgdorferi proteins known to induce borreliacidal antibodies (4,10,11,16,18,19,24,27,28,32). As further support, several patients had inappropriate laboratory results (e.g., IgG antibodies) or clinical or epidemiological findings that suggested an illness other than Lyme disease.…”

Section: Discussionmentioning

confidence: 77%

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Ability of the Borreliacidal Antibody Test To Confirm Lyme Disease in Clinical Practice

Callister

Jobe

Agger

et al. 2002

Clin Vaccine Immunol

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Highly specific borreliacidal antibodies are induced by infection with Borrelia burgdorferi, and a borreliacidal antibody test (BAT) may be an accurate laboratory procedure for confirming Lyme disease in clinical practice. To investigate this, 34 Lyme disease sera and 34 sera from patients with other illnesses who had presented to a primary-care facility located in an area of borreliosis endemicity were tested by the BAT and Western blotting (WB). The BAT was more sensitive (79% versus 65%; P ‫؍‬ 0.090), especially in cases in which patients had a single erythema migrans lesion (P ‫؍‬ 0.021). In addition, the potentially cross-reactive sera were negative by the BAT but WB yielded three (9%) false-positive results. The results from 104 sera from possible Lyme disease patients demonstrated the clinical usefulness of the more sensitive and specific BAT. The BAT was positive for 40 (38%) sera from patients with Lyme disease-related symptoms and appropriate clinical and epidemiological findings. WB confirmed Lyme disease in 30 (75%) of the 40 BAT-positive patients but failed to detect B. burgdorferi infection in 10 BAT-positive patients. WB was also positive for 11 BAT-negative sera, but six (55%) patients had case histories which suggested that the results were false positives. Collectively, the results confirm that the BAT is a sensitive and highly specific test and suggest that widespread use would increase the accuracy of serodiagnostic confirmation of Lyme disease.Lyme disease occurs after the bite of Borrelia burgdorferiinfected Ixodes spp. ticks. Detecting anti-B. burgdorferi antibodies in serum is the most commonly used method for confirming Lyme disease, since detecting the spirochetes by culture or PCR is problematic. The Centers for Disease Control and Prevention (CDC) recommends confirming Lyme disease by a two-tiered system, where serum is screened with an indirect immunofluorescence assay (IFA) or indirect enzymelinked immunosorbent assay. The serum with equivocal or positive results is then confirmed by immunoglobulin M (IgM) and IgG Western blotting (WB) or IgG WB alone if the illness has been present for less than or more than 1 month, respectively (14).WB can accurately confirm Lyme disease (21, 34, 35), especially when patients are tested who reside in a focus of endemicity and present with a tick exposure and well-recognized (13) clinical symptoms. However, false-positive WBs can occur (5, 15, 36) and the impact of the nonspecificity is magnified when the patients have less-typical symptoms or little risk of obtaining a tick bite (26,29,33,35). This shortcoming necessitates the development of a more accurate serodiagnostic test.Infection with B. burgdorferi induces the production of borreliacidal antibodies (6, 9-12, 17, 19, 24, 25, 30-32) that activate complement to form a membrane attack complex. The membrane attack complex then kills the spirochetes without the need for phagocytic cells (4,10,12,(22)(23)(24). Most B. burgdorferi proteins expressed on the surface of the spirochetes induce borrel...

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Section: Discussionmentioning

confidence: 77%

“…The membrane attack complex then kills the spirochetes without the need for phagocytic cells (4,10,12,(22)(23)(24). Most B. burgdorferi proteins expressed on the surface of the spirochetes induce borreliacidal antibodies (4,10,11,16,18,19,24,27,28,32). Unlike other antibodies (e.g., opsonizing), the borreliacidal antibodies are highly specific (9,11,12,19,31).…”

mentioning

confidence: 99%

Ability of the Borreliacidal Antibody Test To Confirm Lyme Disease in Clinical Practice

Callister

Jobe

Agger

et al. 2002

Clin Vaccine Immunol

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“…burgdorferi organisms are easily killed when they bind specific antibody that activates complement (8,31,32). Several outer surface proteins of B. burgdorferi, including OspA, OspB, OspC, and the 39-kDa protein (2,22,(28)(29)(30)33), induce complement-dependent borreliacidal antibody. This feature makes these outer surface proteins ideal candidates for development of a vaccine to prevent infection with B. burgdorferi.…”

Section: Discussionmentioning

confidence: 99%

Gamma Interferon Inhibits Production of Anti-OspA Borreliacidal Antibody In Vitro

Munson

Chateau

Jensen

et al. 2002

Clin Vaccine Immunol

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“…burgdorferi antibodies, especially those directed against outer surface protein A (OspA), OspB, OspC, and the 39-kDa periplasmic protein, have a unique dual function. These antibodies are highly specific for the serodiagnostic identification of infection with B. burgdorferi, and they can kill B. burgdorferi in the presence of complement (2,20,(24)(25)(26)(27). Induction of borreliacidal antibodies is helpful in evaluating the potential of B. burgdorferi vaccines (5,11,22,29).…”

mentioning

confidence: 99%

Production of Borreliacidal Antibody to Outer Surface Protein A In Vitro and Modulation by Interleukin-4

Munson¹,

Chateau

Jobe

et al. 2000

Infect Immun

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Borreliacidal antibody production is one of several parameters for establishing the effectiveness of Borrelia burgdorferi vaccines. The production of borreliacidal antibody was studied in vitro by culturing immune lymph node cells with macrophages and B. burgdorferi. We showed that borreliacidal antibody, directed primarily against outer surface protein A (OspA), was readily produced by lymph node cells obtained from C3H/HeJ mice vaccinated with formalin-inactivated B. burgdorferi in aluminum hydroxide, but not recombinant OspA. AntiOspA borreliacidal antibody was detected in supernatants of cultures of lymph node cells obtained on day 7 after vaccination, peaked on day 17, and rapidly declined. The borreliacidal activity was attributable to immunoglobulin G1 (IgG1), IgG2a, and IgG2b antibodies. When lymph node cells were treated with interleukin-4 (IL-4), production of borreliacidal antibody was inhibited but was unaffected by treatment with anti-IL-4 antibodies. These results suggest that other cytokines, but not IL-4, are mainly responsible for production of the secondary borreliacidal antibody response.Infection with Borrelia burgdorferi, the etiologic agent of Lyme borreliosis, induces a protracted, yet vigorous, humoral immune response (6,8). Most of the anti-B. burgdorferi antibodies involved in this response are important for confirming the clinical diagnosis of Lyme borreliosis (6,8,9), while they play a minor role in protecting the host against infection. Furthermore, several of these anti-B. burgdorferi antibodies, especially those directed against outer surface protein A (OspA), OspB, OspC, and the 39-kDa periplasmic protein, have a unique dual function. These antibodies are highly specific for the serodiagnostic identification of infection with B. burgdorferi, and they can kill B. burgdorferi in the presence of complement (2,20,(24)(25)(26)(27). Induction of borreliacidal antibodies is helpful in evaluating the potential of B. burgdorferi vaccines (5,11,22,29).Recently, clinical trials of two Lyme borreliosis vaccines containing OspA demonstrated that they could protect humans from becoming infected with B. burgdorferi (28, 32). A major concern, however, is the duration of protection afforded by the anti-OspA borreliacidal antibody response. Previously we showed (22) that vaccination with recombinant OspA (rOspA) induced only a short-lived protective borreliacidal antibody response, even after a booster vaccination. Similarly, OspA borreliacidal antibody waned rapidly in hamsters by week 10 of vaccination (22). Thus rOspA or other B. burgdorferi antigens that induce borreliacidal antibodies must be capable of maintaining sustained high levels of borreliacidal antibodies. This would reduce the number of vaccinations required for induction of borreliacidal antibody and lessen the potential for developing adverse side effects that may resemble arthritis (7). Recently, we showed that severe destructive arthritis could be elicited in vaccinated animals challenged with B. burgdorferi only during periods w...

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Animal and human antibodies reactive with the outer surface protein A and B of Borrelia burgdorferi are borreliacidal, in vitro, in the presence of complement

Cited by 15 publications

References 19 publications

Ability of the Borreliacidal Antibody Test To Confirm Lyme Disease in Clinical Practice

Ability of the Borreliacidal Antibody Test To Confirm Lyme Disease in Clinical Practice

Gamma Interferon Inhibits Production of Anti-OspA Borreliacidal Antibody In Vitro

Production of Borreliacidal Antibody to Outer Surface Protein A In Vitro and Modulation by Interleukin-4

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