Babesia antigen detection assay for blood screening

用于血液筛查的巴贝虫抗原检测试验

• 批准号: 9043951
• 负责人: Andrew E. Levin
• 金额: $ 99.52万
• 依托单位: IMMUNETICS, INC.
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-01 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9043951
• 关键词: Acute; Agreement; Algorithms; Antibodies; Antibody Response; Antigens; Area; Babesia; Babesia microti; Babesiosis; Biological Assay; Bite; Blood; Blood Donations; Blood Screening; Blood Transfusion; Blood donor; Blood donor screening; Blood specimen; Borrelia microti; Clinical; Clinical Sensitivity; Clinical Trials; Clinical Trials Design; Collaborations; Collection; Contracts; Convalescence; DNA; Deer Tick; Detection; Development; Donor Selection; Enrollment; Enzyme-Linked Immunosorbent Assay; Erythrocytes; Evaluation; Exhibits; Fatal Outcome; Generations; Goals; Gold; Grant; Health; Human; Immunoassay; Immunocompromised Host; In Vitro; Individual; Infection; Intervention; Kinetics; Lead; Licensing; Licensure; Link; Longitudinal Studies; Malaria; Measurable; Methods; Mono-S; Mus; New York; Parasitemia; Parasites; Patients; Peptide Synthesis; Phase; Plasma; Preparation; Prospective Studies; Proteins; Protocols documentation; Rare Diseases; Research; Research Institute; Risk; Safety; Sampling; Sensitivity and Specificity; Series; Serum; Staging; Testing; Time; TimeLine; Transfusion; Universities; Validation; Vascular blood supply; Whole Blood; base; burden of illness; comparative; cost effective; extracellular; follow-up; high throughput screening; meetings; mouse model; novel; polyclonal antibody; prevent; prospective; recombinant peptide; repository; research study; sample collection; systems research; transmission process

 DESCRIPTION (provided by applicant): Human babesiosis is a malaria-like illness caused by infection of red blood cells by the protozoan parasite Babesia microti or related species, primarily transmitted to humans through the bite of infected deer ticks. Babesiosis can also be transmitted by blood transfusion, and is currently acknowledged as the foremost unaddressed infectious risk to the US blood supply. Blood donations from B. microti-endemic areas in the USA can exhibit up to 1% seropositivity, and the distribution of seropositivity is expanding rapidly into adjacent states. Babesiosis has a wide spectrum of clinical presentation with serious to fatal outcome in immunocompromised individuals which includes many transfusion recipients. Undetected Babesia infection in blood donors has been recognized as a serious threat to transfusion safety, with transfusion responsible for over 150 cases since 1979 and a dozen fatalities since 2005. Babesiosis is a "rare disease" by numbers, but with potentially serious to fatal impact on those who acquire it, which significantly contributes to the health burden of this disease. In the absence of other interventions, the only viable strategy to prevent the transfusion of B. microti-contaminated blood units is to screen blood donors for the presence of the parasite. However, no test for Babesia is currently licensed for blood screening and commercially available. Hence there is an urgent and unmet need for blood donor screening to interdict B. microti - contaminated blood donations. This Phase IIb grant will support the development of a Babesia assay based on antigen detection, which will supplement the antibody detection ELISA previously developed under the Applicants' prior Phase II grant. Babesia parasites secrete antigens into the extracellular medium which may be detected in serum or plasma, thus providing a sensitive marker for detection of active infection. In collaboration with consortium partner Tufts University, applicants have identified immunodominant protein antigens which meet these criteria and have generated specific antibodies suitable for antigen capture immunoassay. The antigen capture assay will enable detection of potentially infectious blood donors in the window stage, when antibodies are not yet measurable. Furthermore, it will clear individuals with persistent antibody response due to a previous, resolved Babesia infection to donate blood, eliminating unnecessary and undesirable donor deferrals. The assay will be evaluated on gold standard babesiosis patient samples through collaboration with Yale University, and on 30,000 blood donors through a donor study carried out under IND with consortium partners Blood Systems Research Institute, Creative Testing Solutions and New York Blood Center. The donor study will support a licensure application to FDA for the Babesia test for blood screening. The overall goal is to provide an assay for Babesia microti suitable for high throughput donor screening which will offer the first cost-effective intervention to reduce or eliminate the risk of transfusion-transmitted babesiosis.

 描述（由申请人提供）：人类巴贝虫病是一种疟疾样疾病，由原生动物寄生虫小Babelioti或相关物种感染红细胞引起，主要通过受感染的鹿蜱叮咬传播给人类。巴贝斯虫病也可以通过输血传播，目前被认为是美国血液供应中最重要的未解决的感染风险。来自B的献血。在美国的小杆菌流行区可以表现出高达1%的血清阳性，并且血清阳性的分布正在迅速扩展到邻近的州。巴贝斯虫病有广泛的临床表现，在免疫功能低下的个体（包括许多输血者）中具有严重至致命的结局。献血者中未被发现的巴氏杆菌感染已被认为是对输血安全的严重威胁，自1979年以来，输血造成了150多例病例，自2005年以来有十几例死亡。巴贝西虫病是一种“罕见疾病”，但对感染者有潜在的严重至致命影响，这大大加重了这种疾病的健康负担。在没有其他干预措施的情况下，防止输血的唯一可行策略 的B。被微孢子虫污染的血液单位是为了筛选献血者是否存在寄生虫。然而，目前还没有针对巴氏杆菌的测试被许可用于血液筛查和商业化。因此，迫切需要对献血者进行筛查以阻断B。被微生物污染的献血。该IIb期赠款将支持开发基于抗原检测的巴氏杆菌检测试剂盒，该试剂盒将补充先前在申请人先前的II期赠款下开发的抗体检测ELISA。巴氏疟原虫将抗原分泌到细胞外介质中，其可以在血清或血浆中检测到，从而为检测活动性感染提供灵敏的标记物。在与联盟伙伴塔夫茨大学的合作中，申请人已经鉴定出符合这些标准的免疫显性蛋白抗原，并产生了适用于抗原捕获免疫测定的特异性抗体。抗原捕获检测将能够在窗口阶段检测潜在感染性献血者，此时抗体尚未可测量。此外，它将清除由于先前已解决的巴氏杆菌感染而具有持续抗体反应的个体献血，消除不必要和不希望的供体延迟。通过与耶鲁大学的合作，将对金标准巴贝西虫病患者样本进行评估，并通过与联盟合作伙伴血液系统研究所，创新测试解决方案和纽约血液中心在IND下进行的30，000名献血者研究进行评估。该供体研究将支持向FDA申请用于血液筛查的巴氏试验的许可证。总体目标是提供一种适用于高通量供体筛选的小巴贝斯虫检测方法，这将提供第一种具有成本效益的干预措施，以减少或消除输血传播的巴贝斯虫病的风险。