Excivion Ltd who’re a biotechnology firm growing novel vaccines primarily based on its proprietary glycan-cloaking molecular design and adjuvant platforms, at this time proclaims the publication of a peer-reviewed article in Frontiers in Immunology (Echegaray et al. July 23, 2021, doi: 10.3389/fimmu.2021.703887) which demonstrates the distinctive efficiency benefits and flexibility of its novel antigen and system design improvements embodied within the type of lateral movement antibody exams for dengue and Zika.
Dengue is a pandemic illness affecting at the very least 120 tropical nations and, more and more, subtropical nations – a development that’s more likely to enhance with international warming. Dengue is accountable for fever and haemorrhagic illness. An estimated 105 million dengue infections happen every year, leading to 500,000 hospitalisations and 44,000 deaths. There isn’t a particular therapy for extreme dengue, solely supportive care akin to IV fluids or blood transfusion. Though vaccines have been developed in opposition to dengue, the primary of those (DengvaxiaÒ) is really helpful just for individuals who have beforehand been contaminated with dengue, or in extremely endemic territories the place prior an infection could also be assumed.
“It’s because the vaccine can prime for extreme dengue in dengue-naïve topics, which is extremely undesirable. Just lately it was additionally demonstrated (Katzelnick et al PMID 32855339) that Zika an infection (like dengue an infection) can prime for extreme dengue and, to date, the priming impact of prior Zika vaccination on the dangers of dengue vaccination (useful or in any other case) just isn’t recognized. These are compelling causes for the event of improved point-of-care antibody exams (as advocated by WHO) that will inform vaccination apply with dengue (and Zika) vaccines. At present there isn’t any licensed Zika vaccine.
“We got down to develop novel antibody diagnostic exams for prior dengue and Zika primarily based on our proprietary glycan-cloaked envelope proteins from dengue and Zika, which ship improved specificity by concealing the extremely cross-reactive fusion loop. The idea borrows from the immune stealth side of HIV’s ‘spike’ protein gp120, the place its ample glycans kind a molecular capsule that thwarts antibody recognition. The identical stealth precept is exploited by COVID. Right here we utilized this idea in a localised approach to the fusion loop of the envelope proteins, ‘borrowing a leaf’ from HIV, one may say by planting the fusion loop with glycans.
“Nonetheless, we have been disenchanted with the sensitivity of present check architectures and, felt compelled to invent a extra delicate check structure befitting the sensitivity wants of detection of historic dengue. These twin improvements, that’s the glycan cloaking and the check structure, have been key to the profitable improvement of the superior check. Beforehand, lateral movement antibody exams had been designed to diagnose ongoing dengue and Zika infections, at which era antibody ranges are excessive. The brand new exams enable the detection of legacy concentrations of antibodies indicative of prior an infection, that are rather a lot decrease. That is vital for the usage of vaccines, by figuring out topics who’re safely eligible to obtain them.” Stated Peter Laing CEO of Excivion and inventor of the patents.
Excivion’s granted patents in Europe and the USA (Granted European Patent No. EP3458471B1, Granted US Patent No. 11,028,133 B2) present composition of matter protection for glycan-cloaked flavivirus antigens protecting all positions within the fusion loop which is 100% conserved throughout all main human flavivirus pathogens (Zika, dengue 1-4, Japanese encephalitis virus and yellow fever virus). These patents cowl the diagnostic in addition to the vaccine utility of the antigens. As well as, Excivion has a pending patent (within the US and elsewhere) on the novel lateral-flow check structure for flaviviruses usually, which options quite a few improvements over and above the usage of hyperglycosylated antigens.
These embody: the arrest of antigen within the check by way of an appended tag by way of an immobilised anti-tag antibody (avoiding competitors with antibodies in opposition to flaviviruses current within the pattern that might in any other case attenuate sign); additionally the disposition of antigens within the fluid section of the operating check which optimises the situations for antigen interplay with antibodies of the pattern; and the inclusion of off-target antigens missing an appropriate tag, in an effort to get rid of false positives as a result of cross-reactivity at websites exterior the fusion loop. The knowhow of the novel check structure has been licensed to Coronex Ltd for COVID lateral-flow exams the place it confers the identical benefits as for dengue and Zika serology.
“The analysis of the exams was performed in collaboration with the teams of Dr. Leah Katzelnick of the Nationwide Institute of Allergy and Infectious Illnesses (NIAID), a part of the Nationwide Institutes of Well being, Dr. Eva Harris and Dr. Josefina Coloma of Berkeley Faculty of Public Well being, Dr. Shuenn-Jue Wu of the Naval Medical Analysis Heart in Maryland, and Dr. Phil Cooper of St George’s within the UK. Whereas their involvement doesn’t indicate any endorsement of the exams, their formidable experience was key to conducting an efficient analysis, and understanding how finest to make use of the exams. The analysis concerned the usage of well-characterised panels of PCR-proven circumstances of dengue and Zika, together with research of endemic populations of Nicaragua and Ecuador.
“The Excivion dengue lateral movement exams enable an unprecedented diploma of sensitivity and specificity. The dengue lateral movement check was as delicate as 5 industrial dengue antibody ELISAs, a few of which make no distinction between Zika and dengue, however furthermore was extremely particular for dengue, versus its closest relative, Zika. The Zika lateral-flow check was likewise extremely particular and delicate (>98% and >93% respectively) for Zika antibodies, permitting dependable identification of prior Zika. At Excivion we consider that the novel antigens and check structure are a sport changer, significantly as a result of the antigens can be utilized in laboratory exams in addition to point-of-care exams for detection of ongoing or historic dengue and Zika, and we at the moment are searching for manufacturing collaborators and licensing companions for our patents world-wide.”