Continuing challenges for Zika virus diagnostics as we move into 2017
Although the formal Public Health Emergency for Zika virus infection has been declared over, the virus continues to present major challenges to global healthcare networks.
The virus continues to spread to new areas, having been reported for the first time in Texas and
also in Angola in the last month. In total, this outbreak has seen more than 500,000 cases reported worldwide, and more than 2,600 confirmed cases of Zika congenital syndrome.
Alongside challenges in therapy and in vaccine research, the development of accurate Zika diagnostics has been a major challenge. A significant number of PCR tests to detect acute infection have been developed and approved under Emergency Use Authorisations (EUA) by the FDA. However, the window for detecting Zika infection by PCR is very short, and these tests are not always available in the areas where Zika infection is most problematic. There remains a real need for accurate and sensitive serological assays to detect Zika infection, and only two such assays have received EUAs from the FDA. One of these is not a commercial product (the CDC Zika MAC-ELISA), and the other (the InBios ZIKV Detect IgM ELISA) has recently suffered from reports of high false-positive rates when compared to the reference CDC assays.
So, why has progress with serological Zika diagnostics been so slow? Probably the major challenge is that Zika is so closely related to Dengue virus, and therefore developing assays that do not cross-react with Dengue virus is extremely challenging. This is particularly important as geographically Zika is found in areas that have very high levels of endemic Dengue infection, and the majority of patients have previously suffered from Dengue. In such cases, it can be very difficult to distinguish a new Zika infection from infection with Dengue.
Assay developers have been looking for the best Zika virus antigen to base their tests on. There has been a focus on the NS1 antigen and more recently on Envelope antigens, and commercial tests based on both of these antigens have been developed, as well as assays published by academic groups. At The Native Antigen Company we have been at the forefront of developing these antigens for assay development for Zika diagnostics, and offer developers a wide range of options to use within their assays.
We express our NS1 protein in a mammalian system, which results in it being glycosylated and assembled in hexameric format in the same way as native antigen. Alongside Zika NS1 (from both Uganda and Suriname strains), we offer NS1 from each of the Dengue virus serotypes, and a range of other flaviviruses, thus permitting in-depth analysis of cross-reactivity within assays.
Also expressed in our mammalian system, we now have available Envelope protein from both Zika and Dengue virus.
Our Zika and Dengue VLPs are recombinant proteins, containing multiple copies of Envelope and prM/M proteins. These make them excellent antigens for assays demanding maximum sensitivity.
Alongside our recombinant proteins, we also offer two different preparations containing native Zika virus proteins. These have been prepared from cultures of Zika infected Vero cells. The first of these contains purified inactivated Zika virus, prepared by ultracentrifugation, and comprising a range of structural proteins including Capsid, Membrane and Envelope proteins. Our second native Zika product is derived from the debris of infected Vero cells, and contains both structural and a range of non-structural proteins including NS1, NS3 and NS5.
As a complement to our antigen range for Zika diagnostics, we also offer a number of monoclonal antibodies that are specific for Zika NS1 protein. These antibodies do not cross-react with NS1 from other flaviviruses.
All of these products are available both to researchers and to commercial assay developers. They are further complemented by antigens from Chikungunya virus, which is also prevalent in Zika infected areas and must be excluded from any differential diagnosis. Further antigens related to viral infections found in these areas, such as Oropouche virus, are in development and will be released early in 2017.
If you would like to receive more details about any of these reagents please contact us at any time. We are very pleased to continue supporting the development of new and more accurate Zika virus and related assays.