Excivion confirms success of point-of-care dengue and Zika antibody tests with ‘invisibility cloak’ technology
Cambridge biotechnology company Excivion has confirmed positive results for its dengue and Zika antibody tests, which employ ‘invisibility cloak’ technology.
The St John’s Innovation Centre business describes the performance advantages of the novel point-of-care lateral flow tests in a peer-reviewed article in the journal Frontiers in Immunology.
The mosquito-borne pandemic disease dengue affects 120 tropical countries and increasingly subtropical countries - a trend expected to continue amid global warming. It causes an estimated 105 million infections each year, leading to 500,000 hospitalisations and 44,000 deaths, and there is no specific treatment for severe dengue - only supportive care such as IV fluids or blood transfusions.
The first vaccine for it, DengvaxiaÒ, is only recommended those who have previously been infected with dengue, or in highly endemic territories where prior infection can be assumed, because the vaccine can prime for severe dengue in dengue-naïve subjects.
Recent studies have shown that Zika infection - a close relative, also spread by mosquitoes - can also prime for severe dengue but so far, the priming effect of prior Zika vaccination on the risks of dengue vaccination is unknown.
This means point-of-care antibody tests that can inform vaccination practice with dengue and any forthcoming Zika vaccines are much in demand. Currently there is no licensed Zika vaccine.
Peter Laing, CEO of Excivion and inventor of the patents, told the Cambridge Independent: “We have been inspired by Harry Potter to make an ‘invisibility cloak’ for a viral antigen. A technique that could have many uses in virology, anticipating and thwarting pandemics.
He explained: “We set out to develop novel antibody diagnostic tests for prior dengue and Zika based on our proprietary glycan-cloaked envelope proteins from dengue and Zika, which deliver improved specificity by concealing the highly cross-reactive fusion loop.
“The concept borrows from the immune stealth aspect of HIV’s ‘spike’ protein gp120, where its abundant glycans form a molecular capsule that thwarts antibody recognition. The same stealth principle is exploited by Covid.
“Here we applied this concept in a localised way to the fusion loop of the envelope proteins, ‘borrowing a leaf’ from HIV, one might say by planting the fusion loop with glycans.
“However, we were disappointed with the sensitivity of existing test architectures and, felt compelled to invent a more sensitive test architecture befitting the sensitivity needs of detection of historic dengue. These twin innovations, that is the glycan cloaking and the test architecture, were key to the successful development of the superior test.
“Previously, lateral flow antibody tests had been designed to diagnose ongoing dengue and Zika infections, at which time antibody levels are high. The new tests allow the detection of legacy concentrations of antibodies indicative of prior infection, which are a lot lower.
“This is important for the use of vaccines, by identifying subjects who are safely eligible to receive them.”
Independent tests showed the Excivion dengue lateral flow tests allow an unprecedented degree of sensitivity and specificity. It proved as sensitive as five commercial dengue antibody ELISAs, some of which make no distinction between Zika and dengue. By contrast Excivion’s test was highly specific for dengue.
The Zika lateral-flow test was likewise highly specific (more than 98 per cent) and sensitive (more than 93 per cent) for Zika antibodies, allowing reliable identification of prior Zika.
“At Excivion we believe that the novel antigens and test architecture are a game changer, particularly because the antigens can also be used in laboratory tests as well as point-of-care tests for detection of ongoing or historic dengue and Zika, and we are now seeking manufacturing collaborators and licensing partners for our patents worldwide,” said Peter.
Excivion’s work on flavivirus diagnostics is funded by the Department of Health and Social Care as part of the UK Vaccine Network (UKVN), a UK Aid programme. The company is also developing vaccines.
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