Detects and Differentiates between Zika Virus and Dengue Virus
A New York State Clinical Laboratory Evaluation Program (CLEP) approved assay demonstrates the ability to address an unmet need. Results from commonly used serologic assays are often confounded due to the cross reactivity among flaviviruses.
Developed by scientists at the New York State Department of Health Wadsworth Center and the University of Texas Medical Branch, the assay outperforms single antigen/antibody ZIKV IgM-Capture ELISA testing in overall sensitivity, specificity, positive predictive value and negative predictive value by detecting IgG-IgA-IgM antibodies to Zika Virus (ZIKV) and Dengue virus (DENV) serotypes 1-4. In one study the assay demonstrated over 50% higher sensitivity.
ZIKV infection continues to be a significant global public health concern. Although the number of locally transmitted Zika cases has lessened where much of the endemic population has developed immunity, Zika still thrives in populations that have yet to be hit by the first wave of transmission, leading to flare-ups and travel-related cases. Although ZIKV is spread primarily through mosquito bites, it can also spread through sexual contact. Many people infected with ZIKV have no symptoms, or only have mild symptoms. For this reason, travelers to an area with risk of ZIKV can unknowingly be infected with ZIKV and pass it to sexual partners months after infection. This means ZIKV is a concern not only for women who are pregnant or may become pregnant, but also for their partners and offspring. Unlike DENV, ZIKV infections during pregnancy correlate with severe defects, including microcephaly and neurological disorders. Because ZIKV and DENV are related flaviviruses, their homologous proteins and nucleic acids can cause cross-reactions and false positive results in molecular, antigenic and serologic diagnostics. Since ZIKV, DENV and other flaviviruses including chikungunya, an arbovirus, co-circulate in the same regions, a positive result for one of these viruses does not preclude infection with the others. The assay provides the broadest spectrum of information to be captured in light of the clinical picture, any travel history and timing of specimen collection for addressing suspected flavivirus infections.
New York State Clinical Laboratory Evaluation Program (CLEP) approval was granted in November of 2018.
- Monitoring women who are pregnant or may become pregnant and their partners for presence of ZIKV infection
- Monitoring immune responses in persons with history of residence in or travel to a geographic region with active Zika transmission
- Monitoring response in vaccine trials
- Development of a clinical diagnostic for ZIKV infection
- New York State Clinical Laboratory Evaluation Program (CLEP) approved
- Validated in thousands of samples
- Rapid turnaround time (3 hours)
- Higher throughput and lower cost than ELISA because multiplexing allows use of 50 µg of each recombinant, which produces 2,000 results using a Luminex® 200 instrument (approximately 40 tests per microgram of recombinant protein)
- Outperforms ZIKV IgM Capture-ELISA. In one study:
- Over 57% more sensitive (v. ELISA) in samples containing a mix of ZIKV and/or DENV
- Discriminates between ZIKV and DENV when antibodies to both are present
- Detects DENV immunity in absence of ZIKV infection
- Can be expanded to include Chikungunya virus (CHIKV) detection
- Identifies ZIKV infections in men when IgM is no longer detectable after the convalescent phase; this population is not likely to qualify for access to confirmatory plaque reduction neutralization testing (PRNT) and therefore the virus could go undetected.
Since the initial outbreak of the disease, it has been recognized that the sensitivities and specificities for current ZIKV testing algorithms have shortcomings. Our serologic assay overcomes these barriers by using an antibody-antigen sandwich formed on six Luminex beads with ZIKV envelope, ZIKV NS1, DENV1 NS1, DENV2 NS1, DENV3 NS1 and DENV4 NS1 conjugated to polyvalent IgG+IgA+IgM detector antibodies. *** This is an important distinction since currently serological assays only use ZIKV envelope or ZIKV NS1 antigens, as well as only one antibody, usually IgM, for their diagnostic assays. Also, reliance on the broadly cross-reactive pre-membrane/envelope protein (prM/E) in the Zika IgM ELISA assay causes frequent false-positives. Confirmatory PRNT is expensive, time-consuming (one-week turn-around), has low sample throughput, and uses live virus in the lab, which creates a biosafety risk. Another drawback of PRNT is that it has difficulties distinguishing the infecting virus (primary) in people with, or vaccinated against, a secondary infection.
An extra step in our assay measures IgG antibodies by avidity testing, which determines the time-frame of infection, whether primary or secondary, and is quick and simple. Therefore, our combined approach enables the broadest spectrum of information to be captured in light of the clinical picture, any travel history, and timing of specimen collection.
EBioMedicine 2017 Feb:16: 136-140. Doi: 10.1016/j.ebiom.2017.01.008. Epub 2017 Jan 10
A Multiplex Microsphere Immunoassay for Zika Virus Diagnosis. Wong SJ, Furuya A, Zou J, Xie X, Dupuis AP 2nd, Kramer LD, Shi PY.
U.S. Patent 10,317,413 – Available for license
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