Monoclonal antibodies with in vitro borreliacidal activities define the outer surface proteins A and B of borrelia burgdorferi

Moskophidis, Matthäus; Luther, Birgit

doi:10.1016/s0934-8840(11)80398-1

Cited by 11 publications

(11 citation statements)

References 38 publications

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“…Although vaccination with B. burgdorferi or its components induce protective borreliacidal antibody (1,20,27,28,30,33), the duration of protection is short, less than 8 weeks (24). The development and maintenance of a high level of sustained borreliacidal antibody is paramount for prolonged protection against infection with B. burgdorferi.…”

Section: Discussionmentioning

confidence: 99%

“…These vaccine-induced antibodies kill B. burgdorferi in the presence of complement (17,24). Specifically, it has been shown that antisera raised against recombinant outer surface protein OspA can prevent borrelial infection by passive immunization (8,17,31,34), kill B. burgdorferi in vitro (13,17,18,20,24,27,29,30), and sterilize B. burgdorferi-infected ticks (11). However, anti-OspA borreliacidal activity wanes rapidly after active immunization.…”

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confidence: 99%

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Neutralization of Gamma Interferon Augments Borreliacidal Antibody Production and Severe Destructive Lyme Arthritis in C3H/HeJ Mice

Munson

DeCoster

Nardelli

et al. 2004

Clin Vaccine Immunol

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Development of a high level of sustained borreliacidal antibody is paramount for maintaining protection against infection with Borrelia burgdorferi. We show that production of borreliacidal antibody can be enhanced by preventing the effects of gamma interferon (IFN-␥). When lymph node cells capable of producing borreliacidal antibody were cultured with anti-murine IFN-␥, an eightfold increase in borreliacidal antibody production was obtained. However, anti-IFN-␥ treatment of these cells also enhanced their ability to adaptively induce arthritis. When anti-IFN-␥-treated lymph node cells producing borreliacidal antibody were infused into C3H/HeJ mice and the mice were then challenged with B. burgdorferi, the mice developed severe destructive Lyme arthritis. Additional studies are needed to delineate the immune response responsible for the induction of arthritis and production of borreliacidal antibody. These studies are needed to ensure an effective and safe vaccine against infection with B. burgdorferi.Vaccination with Borrelia burgdorferi or its components can induce antibodies that prevent infection with the Lyme disease spirochete (1, 6, 8-10, 13, 27, 34). These vaccine-induced antibodies kill B. burgdorferi in the presence of complement (17,24). Specifically, it has been shown that antisera raised against recombinant outer surface protein OspA can prevent borrelial infection by passive immunization (8, 17, 31, 34), kill B. burgdorferi in vitro (13, 17, 18, 20, 24, 27, 29, 30), and sterilize B. burgdorferi-infected ticks (11). However, anti-OspA borreliacidal activity wanes rapidly after active immunization. Padilla et al. (24) reported that vaccination of experimental animals with recombinant OspA induced a borreliacidal antibody response that peaked 6 weeks after vaccination and declined rapidly. Moreover, human volunteers administered several doses of recombinant OspA produced borreliacidal antibody that rapidly decreased (24). Only one vaccinee had antibody 6 months after vaccination. The poor OspA-borreliacidal antibody response may have been a factor in prompting withdrawal of the vaccine for use in humans.Very little is currently known about the immunologic events that might promote and maintain a sustained borreliacidal antibody response after vaccination. Therefore, we developed an in vitro system to determine the effects of immunological mediators on production of borreliacidal activity. Several cytokines have been evaluated, including interleukin (IL)-4, a known B-lymphocyte stimulator (26), and its antagonist, gamma interferon (IFN-␥) (25). However, these cytokines failed to induce high levels of borreliacidal antibody (21, 22).Here, we report that treatment of lymph node cells containing borreliacidal antibody-producing cells with anti-murine IFN-␥ augments the production of anti-B. burgdorferi antibody. Unfortunately, treatment of these cells with anti-murine IFN-␥ also enhances their ability to induce arthritis. MATERIALS AND METHODSMice. Inbred C3H/HeJ mice 8 to 12 weeks old were obtained fro...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Neutralization of Gamma Interferon Augments Borreliacidal Antibody Production and Severe Destructive Lyme Arthritis in C3H/HeJ Mice

Munson

DeCoster

Nardelli

et al. 2004

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).…”

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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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Monoclonal antibodies with in vitro borreliacidal activities define the outer surface proteins A and B of borrelia burgdorferi

Cited by 11 publications

References 38 publications

Neutralization of Gamma Interferon Augments Borreliacidal Antibody Production and Severe Destructive Lyme Arthritis in C3H/HeJ Mice

Neutralization of Gamma Interferon Augments Borreliacidal Antibody Production and Severe Destructive Lyme Arthritis in C3H/HeJ Mice

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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