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Rapid Diagnostic Assay for Antibody Dependent Enhancement Following Secondary Flaviviruses Infection



In recent years, Flaviviruses such as Zika virus (ZIKV), Dengue, Chikungunya, West Nile, Yellow Fever, Japanese Encephalitis and Tick-Borne Encephalitis were responsible for many cases of diseases. The 2014-2016 large outbreak of ZIKV in Latin America was accompanied with cases of microcephaly in newborns which were not reported in Africa, in-spite of the fact that ZIKV has already been circulating in Africa for >50 years. Recent findings suggest that this effect may be associated with antibody-dependent enhancement (ADE) due to previous exposure to other Flaviviruses such as Dengue, which exists in Latin America, but not in Africa. This raises the concern that Flaviviruses vaccines including yellow fever and Tick Born Encephalitis (TBE), may also increase the risk following ZIKV infections. A recent study has provided evidence for the correlation between anti-Dengue antibody titers and the severity of secondary Dengue infections. Therefore, a serological detection tool of anti-Flavivirus antibodies may predict the severity of a new Flavivirus infection.


The Technology


Using a unique cohort of TBE vaccinated and naturally infected subjects collected in Siberia, we have shown in-vitro that previous vaccination or infection with TBE significantly increases the risk of ADE upon secondary infection with the ZIKV (Figure). Nonetheless, this scenario is more complicated since not all the vaccinated individual developed ADE to ZIKV, suggesting a better predication method is highly needed.  For that end, we aim to develop a rapid serological–based diagnostic assay to assess the risk of developing ADE upon secondary infection with a Flavivirus. Based on our preliminary data, we foresee that the titer of cross-reactive anti-Flavivirus antibodies that are induced by previous vaccination or infection will be a good predictor for ADE risk.




  • There are multiple uses for the KIT including; (1) assessing ADE risk in pregnant women; (2) identify risk of complications following ZIKAV infection; (3) study the correlation between previous exposures to flavivirus infections and vaccines and the risk for embryo defects using clinical samples from ongoing studies in South America; and (4) study the safety profile of Flavivirus vaccines.
  • The Kit based on A rapid, cost-effective antigen microarray that can simlutaneously test antibody binding for all Flaviviruses using minimal amounts of serum samples.
  • The assay will be supported by A prediction algorithm that will identify the specific cross-reactivity profiles associated with ADE.


Patent status

Provisional patent No. 62/945,179 filed December 8, 2019


Principal Investigator


Prof. Tomer Hertz, NIBN and the Shraga Segal Department of Microbiology, Immunology and Genetics, Ben-Gurion University of the Negev, Israel