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New Zika-Specific Synthetic Biomarker Can Differentiate From Dengue Virus

A test that identifies Zika distinct from dengue could make a definite impact to expectant mothers and reproductive-age women that are at risk from the mosquito-borne disease.

Researchers have discovered a Zika-specific synthetic molecule which can differentiate patient samples containing Zika antibodies from samples of patients that were infected with dengue virus.

The collaborators from the University of Pittsburgh School of Public Health and The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology have had their findings published in Proceedings of the National Academy of Sciences.

It is difficult to design epidemiological studies or develop diagnostics and vaccines for Zika virus. This is because flaviviruses, the family of viruses that includes Zika and dengue, have been historically difficult to differentiate diagnostically. The diagnostic tests which look for Zika virus antibodies often get confused with dengue virus antibodies which is compounded by the fact that these infections are common in the same geographic areas.

"If you go to places like Brazil, nearly everybody is going to have some immunity to dengue, and also to Zika," says first author Priscila Castanha, Assistant Professor, Department of Infectious Disease and Microbiology, Pitt Public Health.

She continued: "This makes it very difficult to test new treatments or determine how widespread an emerging disease may be in areas endemic for flaviviruses, which cause a high burden of illness globally."

It is important to develop tests that tell reproductive-age women if they have had Zika and are therefore likely immune. It is particularly important that these tests are accurate and differentiate between dengue.

Zika infection during pregnancy can lead to birth defects. Therefore, if a test leads a woman to think they are immune to Zika, when in fact it has detected dengue antibodies, that woman may be less likely to take precautions to avoid Zika virus infection while pregnant.

The team are the first to apply the technology, called an 'epitope surrogate', to Zika, which is encouraging for those working on Zika diagnostics and vaccine development. This technology was developed by the paper's co-author, Thomas Kodadek of UF Scripps.

Here, the team screen around 500,000 peptide-inspired conformationally constrained oligomers (PICCOs), against Zika- or dengue-infected patient blood samples. These PICCOs mimic epitopes in that they can bind to Zika or dengue antibodies, but they are inorganic and can be retrieved after screening.

One particular PICCO stood out to the team, CZV1-1, which attached to Zika antibodies but not dengue. They reported that this PICCO found Zika antibodies 85.3% of the time, with only 1.6% of tests being false positives.

Herein, CZV1-1 can serve as a dengue distinct test for Zika. By investigating the retrieved PICCOs and connected antibodies, the team can tell if the patient has Zika immunity.

"The technology is amazing. You don't need to know the sequence, or the structure, or even the pathogen," said Donald Burke, co-senior author and Dean Emeritus at Pitt Public Health.

He continued: "As long as you have chosen the right sets of patient blood samples to compare, you can tease out the important antibodies that differ between the patient sets, along with the corresponding synthetic molecule biomarkers."