Serologic assays for detection of Zika virus antibodies for clinical diagnosis and blood donor counseling

用于检测寨卡病毒抗体的血清学检测，用于临床诊断和献血者咨询

• 批准号: 10221519
• 负责人: Andrew E. Levin
• 金额: $ 98.93万
• 依托单位: KEPHERA DIAGNOSTICS, LLC
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-18 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10221519
• 关键词: Acute; Address; Aedes; Affect; Africa; Agreement; Antibodies; Antigens; Arboviruses; Area; Awareness; Benign; Biological Assay; Birth; Bite; Blood; Blood Donations; Blood Screening; Blood Transfusion; Blood donor; Caribbean region; Cell Culture Techniques; Centers for Disease Control and Prevention (U.S.); Central America; Clinical; Clinical Research; Collection; Counseling; Culicidae; Dengue; Dengue Infection; Dengue Virus; Detection; Development; Diagnostic; Discrimination; Disease Outbreaks; Early Diagnosis; Ensure; Enzyme-Linked Immunosorbent Assay; Epidemic; Epidemiology; Epitopes; Event; Exposure to; FDA Emergency Use Authorization; Family; Female; Flavivirus; Freezing; Funding; Generations; Geography; Grant; Guillain Barré Syndrome; Health; Human; Immunoglobulin G; Immunoglobulin M; Individual; Infant; Infection; International; Investigation; Japanese Encephalitis; Laboratories; Life; Link; Meningitis; Mexico; Microcephaly; Monitor; Mutation; Neurologic; Neutralization Tests; Nucleic Acid Amplification Tests; Nucleic Acids; Performance; Phase; Plasma; Population; Pregnant Women; Preparation; Procedures; Product Approvals; Production; Protocols documentation; Public Health; Puerto Rico; Ramp; Readiness; Recombinants; Recurrence; Reproducibility; Research; Research Design; Research Institute; Risk; Sampling; Serology; Serology test; Serum; Sexual Transmission; South America; Specificity; Spottings; Techniques; Testing; Time; Translating; Translations; Travel; United States; United States Food and Drug Administration; Vascular blood supply; Viral; Viremia; Virus; Virus Diseases; West Nile virus; Woman; World Health Organization; Yellow Fever; ZIKA; ZIKV infection; Zika Virus; adverse outcome; antibody test; authority; base; clinical Diagnosis; clinical diagnostics; congenital zika syndrome; cross reactivity; design; detection assay; detection sensitivity; diagnostic assay; disability; falls; in-vitro diagnostics; manufacturing scale-up; mosquito-borne; pathogenic virus; pre-clinical; preclinical study; prototype; public health emergency; research and development; scale up; secondary infection; seroconversion; stoichiometry; transmission process; validation studies; vector mosquito; viral RNA

PROJECT SUMMARY Zika virus, until recently an obscure mosquito-borne flavivirus from Africa, emerged rapidly in 2015-2016 to pose a major threat to public health in the Western Hemisphere. Having traveled across the Pacific, it quickly became endemic in South and Central America, Mexico and the Caribbean, carried by a compatible Aedes mosquito vector population. While Zika virus infection is typically relatively benign in the acute stage, it is has been causally linked to Congenital Zika Syndrome (CZS) exemplified by microcephaly in infants born to infected women, and to Guillain-Barré syndrome and meningitis. In addition to transmission by mosquito bite, Zika can be transmitted by sexual contact and through blood transfusions. The World Health Organization (WHO) declared Zika to be an international public health emergency, and the U.S. Centers for Disease Control (CDC) and the U.S. Food and Drug Administration (FDA) promptly ramped up efforts to prepare for and respond to the threat posed by Zika in the United States. Accordingly, FDA advised the temporary deferral of blood donors who had potential exposure in endemic areas such as Puerto Rico, and approved the Emergency Use Authorization (EUA) of investigational blood screening assays detecting viral RNA. However, the duration of viremia is very short, such that most individuals exposed to Zika virus are likely to be negative when tested for viral RNA, and the only means to detect prior exposure and associated health risks in such cases is through serologic tests for antibodies to the virus. As the emergence of Zika as a significant human health threat is quite recent, the development of diagnostic assays is still at an early stage, with the first generation of commercial products for serologic testing falling short of ideal performance. A major challenge has been the differentiation of Zika from Dengue virus infection, given that the two viruses are genetically closely related, are carried by the same mosquito vectors, and overlap geographically in regions of endemicity. A large fraction of the endemic population carries IgG to Dengue as a result of prior exposure, and the presence of this background Dengue IgG complicates the detection of Zika antibodies in the same individuals. While the 2015-2016 Zika outbreak has subsided, the potential for a recurrence requires public health readiness, including accurate assays to detect infection. This project addresses the critical need for a highly sensitive and specific serological assay for Zika virus infection that avoids cross- reactivity with Dengue and other viral infections. This assay is needed clinically to identify pregnant women at risk of CZS due to an earlier exposure, as well as epidemiologically to monitor the extent of Zika exposure in a possible outbreak where NAAT testing is impractical due to the time limitations for detection of viremia. In Phase I, we demonstrated feasibility of a prototype assay specific for the Zika virus that accurately distinguished human IgG and IgM antibodies to Zika virus from those elicited by Dengue virus infection. In Phase II, we plan to refine this assay into a commercial product ready for scaled up manufacture, validate it in preclinical studies and prepare for commercial launch for research use and subsequent regulatory submissions for vitro diagnostic use.

项目总结