An antigen-detection assay to diagnose Babesia microti infection

诊断田鼠巴贝斯虫感染的抗原检测方法

基本信息

批准号：
10403621
负责人：
Michel Ledizet
金额：
$ 69.21万
依托单位：
L2 DIAGNOSTICS, LLC
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-01-10 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10403621
关键词：
Acute respiratory failure American Anaplasmosis Animals Antibiotics Antibodies Antigens Babesia Babesia microti Babesiosis Biological Biological Assay Black-legged Tick Blood Blood Transfusion Blood donor Blood specimen Borrelia microti Centers for Disease Control and Prevention (U.S.)Characteristics Clinical Clinical Sensitivity Complex Congestive Heart Failure DNA Development Diagnosis Diagnostic Procedure Diffuse Disease Disease model Elderly Enzyme-Linked Immunosorbent Assay Epitopes Erythrocytes Evaluation Goals Gold Health Human Immunocompetent Immunocompromised Host Immunofluorescence Immunologic Individual Industry Standard Infection Institute of Medicine (U.S.)Kidney Failure Laboratories Lead Longitudinal prospective study Lyme Disease Malaria Methods Microscopic Microscopy Monitor Monoclonal Antibodies Mus Parasitemia Parasites Patients Performance Phase Population Prospective Studies Proteins RNA Recombinant Proteins Recurrent disease Red Cross Relapse Reporting Resolution Retrospective Studies Risk Sampling Sensitivity and Specificity Serology Serum Signs and Symptoms Specificity Statistical Data Interpretation Symptoms Techniques Ticks Transfusion Treatment Failure United States Vascular blood supply active method antibody detection antigen detection assay development base cohort cost design detection assay diagnostic assay experimental study flu granulocyte human disease human model immunosuppressed infection risk mortality mouse model pathogen rapid test tick transmission vector tick

项目摘要

PROJECT SUMMARY Human babesiosis is a malaria-like multisystem disease caused primarily by Babesia microti, an emerging apicomplexan parasite that infects and develops within human erythrocytes. The parasite is transmitted to humans by the tick vector Ixodes scapularis and can also be introduced through blood transfusion. Infection can cause flu-like symptoms, and severe infection can be fatal, in particular in the immunosuppressed and the elderly. Current methods for babesiosis diagnosis include microscopy, PCR, IFA and ELISA-based methods that detect antibodies in serum from patients or donors. Each of these methods has major limitations, such as insufficient sensitivity, high complexity, and low throughput. In addition, results from many of these assays remain positive for months or years after resolution of active infection. In Phase I of this project, we have developed a capture ELISA assay that can detect a protein of the parasite, BmGPI12/BmSAI. We have identified pairs of monoclonal antibodies that can be used to capture BmGPI12 in mouse and human samples. Our preliminary results demonstrate that this assay has an excellent sensitivity. Using samples collected from infected mice, a well-established model of human disease, we demonstrated that following successful treatment, our assay gives negative results while PCR and serology remain positive. Thus, our assay may be useful in distinguishing active infection from past exposure. In Phase II of this project, we will further develop this assay with the goal of applying for FDA clearance. We will analyze several hundred animal and human samples to establish important characteristics of the assay including sensitivity and specificity. These Phase II experiments are designed to give us a full understanding of the potential biological indications and commercial usefulness of the assay.

项目概要人类巴贝虫病是一种类似疟疾的多系统疾病，主要由微小巴贝虫引起，这是一种新兴的巴贝虫病。感染人类红细胞并在其中发育的顶端复门寄生虫。寄生虫被传播到人类通过蜱虫媒介肩胛硬蜱传播，也可以通过输血传播。感染可引起类似流感的症状，严重感染可能致命，特别是在免疫抑制和老年。目前巴贝斯虫病的诊断方法包括显微镜检查、PCR、IFA 和基于 ELISA 的方法检测患者或捐赠者血清中的抗体。这些方法都有很大的局限性，例如灵敏度不足、复杂性高、通量低。此外，许多这些测定的结果活动性感染消退后数月或数年仍呈阳性。在该项目的第一阶段，我们开发了一种捕获 ELISA 检测方法，可以检测寄生虫的蛋白质， BmGPI12/BmSAI。我们已经鉴定出可用于捕获 BmGPI12 的单克隆抗体对小鼠和人类样本。我们的初步结果表明该测定具有出色的灵敏度。使用从受感染的小鼠（一种成熟的人类疾病模型）收集的样本，我们证明了成功治疗后，我们的检测结果呈阴性，而 PCR 和血清学结果仍呈阳性。因此，我们的检测可能有助于区分活动性感染和过去的暴露。在该项目的第二阶段，我们将进一步开发该检测方法，目标是申请 FDA 许可。我们将分析数百个动物和人类样本，以确定测定的重要特征包括敏感性和特异性。这些第二阶段实验旨在让我们充分了解该检测的潜在生物学适应症和商业用途。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Babesia BdFE1 esterase is required for the anti-parasitic activity of the ACE inhibitor fosinopril.

巴贝虫 BdFE1 酯酶是 ACE 抑制剂福辛普利的抗寄生虫活性所必需的。

DOI：
发表时间：
2023-11
期刊：
影响因子：
0
作者：
Vydyam, Pratap;Choi, Jae;Gihaz, Shalev;Chand, Meenal;Gewirtz, Meital;Thekkiniath, Jose;Lonardi, Stefano;Gennaro, Joseph C;Ben Mamoun, Choukri
通讯作者：
Ben Mamoun, Choukri

Specific and Sensitive Diagnosis of Babesia microti Active Infection Using Monoclonal Antibodies to the Immunodominant Antigen BmGPI12.

使用免疫显性抗原 BmGPI12 的单克隆抗体特异性、灵敏地诊断田鼠巴贝虫活动性感染。

DOI：
发表时间：
2022-09-21
期刊：
影响因子：
9.4
作者：
Gagnon, Jacqueline;Timalsina, Sushma;Choi, Jae;Chand, Meenal;Singh, Pallavi;Lamba, Pooja;Gaur, Gauri;Pal, Anasuya C;Mootien, Sara;Marcos, Luis A;Ben Mamoun, Choukri;Ledizet, Michel
通讯作者：
Ledizet, Michel

Tafenoquine-Atovaquone Combination Achieves Radical Cure and Confers Sterile Immunity in Experimental Models of Human Babesiosis.

他非诺喹-阿托伐醌组合在人类巴贝虫病实验模型中实现了根治并赋予了无菌免疫力。

DOI：
发表时间：
2024-01-12
期刊：
影响因子：
0
作者：
Vydyam, Pratap;Pal, Anasuya C;Renard, Isaline;Chand, Meenal;Kumari, Vandana;Gennaro, Joseph C;Mamoun, Choukri Ben
通讯作者：
Mamoun, Choukri Ben

An Alternative Culture Medium for Continuous In Vitro Propagation of the Human Pathogen Babesia duncani in Human Erythrocytes.

用于在人红细胞中连续体外繁殖人类病原体巴贝斯虫的替代培养基。

DOI：
发表时间：
2022-05-20
期刊：
影响因子：
0
作者：
Singh, Pallavi;Pal, Anasuya C;Mamoun, Choukri Ben
通讯作者：
Mamoun, Choukri Ben

Babesia duncani multi-omics identifies virulence factors and drug targets.

邓肯巴贝斯虫多组学鉴定毒力因子和药物靶点。

DOI：
发表时间：
2023-05
期刊：
影响因子：
28.3
作者：
Singh, Pallavi;Lonardi, Stefano;Liang, Qihua;Vydyam, Pratap;Khabirova, Eleonora;Fang, Tiffany;Gihaz, Shalev;Thekkiniath, Jose;Munshi, Muhammad;Abel, Steven;Ciampossin, Loic;Batugedara, Gayani;Gupta, Mohit;Lu, Xueqing Maggie;Lenz, Todd;Chakr
通讯作者：
Chakr