A serologic assay to measure successful Lyme borreliosis antibiotic therapy

描述（由申请人提供）：莱姆病是由蜱虫传播的螺旋体伯氏疏螺旋体感染引起的，是美国最常见的媒介传播疾病，每年向疾病预防控制中心报告的病例超过20,000例。对于莱姆病临床治愈所需的抗生素治疗时间长短存在争议。检测伯氏疏螺旋体抗体的血清学试验（ELISA和免疫印迹）是目前最敏感和最广泛使用的莱姆病实验室试验，但它们不能评估对治疗的反应，也不能区分以前接触过伯氏疏螺旋体和活动性感染。确定抗生素治疗后何时实现实验室治愈仍然是一个巨大的未满足的医疗需求，以区分急性感染或再感染与以前的接触，并防止不必要的长期抗生素治疗。为了满足这一需求，我们在莱姆病小鼠模型中评估了抗生素治疗。我们发现IgG反应在成功的抗生素治疗后迅速下降到伯氏疏螺旋体抗原的一个子集。该I期计划旨在通过蛋白质组学方法改进目前可用的莱姆病血清学检测，该方法将a)识别在抗生素治疗成功后小鼠抗体反应下降的伯氏疏螺旋体抗原，b)评估其在区分活动性感染和抗生素治愈感染方面的诊断潜力。滴度下降或对抗原反应性丧失将与抗生素灭菌相关，这将通过多种措施得到证实。候选诊断抗原将以重组蛋白的形式生产，并在不同感染阶段接受抗生素治疗的小鼠血清和代表不同阶段伯氏疏螺旋体感染的患者血清中检测反应性。这些诊断测试在患者中的特异性和敏感性将在II期确定，预测抗生素成功消除感染的定量ELISA检测将开发用于商业临床实验室。

DESCRIPTION (provided by applicant): Lyme disease, due to infection with the Ixodes tick-transmitted spirochete Borrelia burgdorferi, is the most common vector-borne disease in the United States, with over 20,000 cases reported to the CDC annually. There is controversy over the length of antibiotic therapy that is necessary to achieve a clinical cure for Lyme disease. Serologic tests (ELISA and immunoblot) that detect antibodies against B. burgdorferi are currently the most sensitive and widely available laboratory tests for Lyme disease, but they do not assess response to therapy and can not distinguish previous exposure to B. burgdorferi from active infection. The determination of when a laboratory cure is achieved after antibiotic treatment remains a large, unmet medical need for distinguishing acute infection or re-infection from previous exposure and for preventing unnecessary treatment with long-term courses of antibiotics. To address this need, we have assessed antibiotic therapy in the mouse model of Lyme borreliosis. We found that IgG responses decline rapidly to a subset of Borrelia antigens after successful antibiotic therapy. This Phase I proposal seeks to improve upon the currently available serologic tests for Lyme disease through a proteomic approach that will a) identify the B. burgdorferi antigens to which murine antibody responses decline after successful antibiotic treatment and b) evaluate their diagnostic potential in distinguishing active infections from those cured with antibiotics. Declines in titer or loss of reactivity to the antigens will be correlated with antibiotic sterilization that will be confirmed by multiple measures. The candidate diagnostic antigens will be produced as recombinant proteins and tested for reactivity with sera from mice treated with antibiotics at different stages of infection and patient sera representative of various stages of B. burgdorferi infection. The specificity and sensitivity of these diagnostic tests in patients will be determined in Phase II, and quantitative ELISA assays that predict successful elimination of infection by antibiotics will be developed for use in commercial clinical laboratories. PUBLIC HEALTH RELEVANCE: Lyme disease is an infection with the tick-transmitted spirochete Borrelia burgdorferi. Some people have lingering symptoms even after antibiotic therapy, and there is no test to determine the effectiveness of antibiotics at eliminating the infection. Our intent is to significantly improve the evaluation of patients treated for Lyme borreliosis through the introduction of new serologic tests that predict when infection has been cured and distinguish prior exposure from active infection.