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Responding to Zika Threat, Dx Companies Employing a Variety of Technologies in Test Development

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NEW YORK (GenomeWeb) – Diagnostics companies are drawing on capabilities in molecular and antibody test development to combat the threat of an increasing volume of Zika virus infections.

"Almost everybody agrees that we are really just at the beginning of the Zika problem, and we are going to need a lot of different approaches to control Zika including mosquito control, vaccination, and diagnostics," Mark Miller, BioMérieux's chief medical officer, told GenomeWeb. "Diagnostics are going to be key here because of the type of infection that Zika is and because so many of the patients are asymptomatic."

BioMérieux's strategy to tackle Zika includes the development of molecular and serology tests. Each has its place depending on the clinical need, Miller said.

Molecular tests are very useful for those who present, for example, with symptoms of a compatible syndrome with Zika and where you want to rule in or rule out a pathogen, Miller said. Serology, on the other hand, will be most useful to screen pregnant women for Zika and determine who is most susceptible.

"For those who are susceptible, they will need to be monitored because many of the infections are asymptomatic and you will not have any other way to detect them," Miller added.

The BioFire Defense business of BioMérieux is developing its Zika molecular test on the firm's FilmArray, an automated testing system that uses PCR and melt-curve analysis and simultaneously tests for multiple infectious agents in a single panel from a positive blood culture in about an hour. FilmArray currently tests for 27 targets, including gram positive bacteria, gram negative bacteria, yeast, and antibiotic-resistant genes.

The real strength of the FilmArray platform is its highly multiplexed syndromic approach, in which its panels have many different targets for infectious disease, according to BioMérieux. "We are developing a Zika test, but our intention is to have Zika as part of a syndromic panel where various pathogens all related to the same type of syndrome can be ruled in or ruled out with a single test," Miller said.

In May, BioMérieux began discussing the molecular Zika test with the US Food and Drug Administration with a view to obtaining an emergency use authorization, Miller said. Earlier, in March, the firm began developing the serologic test including IgG and IgM versions. Development of the serology test is more difficult and takes longer than a molecular test, Miller said. However, the goal is to submit an application to the FDA for an EUA for both tests.

Because anti-Zika antibodies appear in the body soon after infection and are present in the body for longer periods than the virus, executives at OraSure Technologies said they believe there is a significant need and utility for a rapid Zika antibody test. Earlier this year, the company engaged in a development program for rapid Zika assays on its OraQuick platform and said that it was actively pursuing external funding to advance this program.

Last week, the firm announced that it has been awarded a contract by the Biomedical Advanced Research and Development Authority (BARDA) of the US Department of Health and Human Services worth up to $16.6 million to advance its rapid Zika tests. OraSure and HHS inked a six-year, multi-phased contract that includes an initial commitment of $7 million and options for up to an additional $9.6 million to fund the evaluation of product enhancements, and clinical and regulatory activities, OraSure said.

"Although there are currently molecular tests available for Zika, we believe these tests have limited utility because of the short window of time when viral RNA can be detected in patients," Mike Reed, OraSure Technologies' chief science officer, told GenomeWeb. "Because anti-Zika antibodies appear in the body soon after infection and are present in the body for longer periods than the virus, we believe there is a significant need and utility for a rapid Zika antibody test."

OraSure's products are serological tests that use a lateral flow technology similar to a pregnancy test. Serological tests look for antibodies produced by the body's immune response to viruses, Reed said, and the body produces the earliest response to the Zika virus beginning approximately two weeks after infection and up to three months later.

"Serological tests are critical in determining whether someone recently was infected with Zika because most people who are infected with the virus do not develop clinical symptoms," Reed added. "Without such symptoms, they are unlikely to seek testing while the virus is present in their blood and detectable by current available diagnostic tests."

The firm's lateral flow tests can be performed in a doctor's office. Because they don't need to be sent to a laboratory, there are no long delays in getting test results, and the anxiety associated with the uncertainty during wait times is avoided, Reed added. And laboratory tests can take from days to two weeks for results, while rapid tests are typically conducted in 20 to 30 minutes.

OraSure also expects to seek an Emergency Use Authorization for its test from the FDA.

In addition to the OraSure test, BARDA is supporting the development of several other diagnostic tests for Zika, with the objective of making the tests available sooner and at potentially lower cost than if the tests were developed without federal funding. They include serological tests being developed by DiaSorin and InBios designed for use in commercial and healthcare facility laboratories, and a molecular test being developed by Hologic for use in blood banks.

In February and March, the FDA cleared two CDC assays under Emergency Use Authorizations. The first was the CDC Zika IgM Antibody Capture Enzyme-Linked Immunosorbent Assay, or Zika MAC-ELISA. Laboratory staff use it to detect Zika virus-specific IgM in human sera or cerebrospinal fluid that's submitted alongside a patient-matched serum specimen. According to the CDC, anti-Zika IgM is typically detectable starting soon after the onset of symptoms and for about 12 weeks after infection.

But Kelly Wroblewski, director of infectious diseases at the Association of Public Health Laboratories in Silver Spring, Maryland, recently told GenomeWeb that the MAC-ELISA is a very labor-intensive assay with low throughput and without automation.

The second diagnostic test to receive an EUA was the CDC's Trioplex, a real-time RT-PCR assay used for the qualitative detection and differentiation of RNA from Zika virus, dengue virus, and chikungunya virus in human sera or cerebrospinal fluid.

Since March, a range of Zika tests have received EUAs. As reported by GenomeWeb, tests developed by Siemens Healthcare Diagnostics, Viracor-IBT, Hologic, Altona Diagnostics, and Quest Diagnostics have all received the EUA label. And earlier this week, the FDA granted an EUA to a Zika test from Roche that runs on the firm's LightCycler 480 Instrument II or Cobas z 480 Analyzer.

The LightMix Zika real-time RT-PCR Test is an easy-to-use molecular diagnostic test that enables healthcare professionals to quickly detect viral RNA in plasma or serum of patients meeting US Centers for Disease Control and Prevention clinical or epidemiological criteria, Roche said in a statement.

In March, Roche had already received FDA approval to initiate collection and testing of blood samples for screening with the Cobas Zika assay under an Investigational New Drug Application protocol.

OneBlood, a non-profit organization that provides blood to hospitals throughout most of Florida, began using the Roche assay running on the Cobas 8800 and 6800 test platforms on samples from Puerto Rico on April 1.

A revised guidance from the US Food and Drug Administration last week recommended universal testing of donated whole blood and blood components for Zika virus in the US and its territories, which could spur the development of additional molecular tests.

"Blood screening is a whole different kettle of fish," BioMérieux's Miller said, "that requires a highly sensitive molecular test with high throughput. We're not developing something for that particular application, but as Zika becomes more widespread there will be requirements by various countries to do blood screening for Zika from blood donations. That's going to be one additional diagnostic test that will be required to control Zika."

Whether countries enact blood donor screening or not is a public health policy decision, he said, and it needs to be balanced between weighing medical need, health economics and the population, and how endemic or epidemic the pathogen is.

"It's up to each government to decide," Miller said. "As a diagnostics company, we are definitely of the opinion that diagnostics are key to try to control Zika."