Research Kevin Ariën

Abstract

The number of outbreaks of arboviruses, such as Dengue, Chikungunya and Zika, is increasing globally. These viruses are mainly transmitted by mosquitos in (sub)tropical regions and are responsible for a significant public health burden. Importantly, the population growth, urbanisation and climate change lead to an increase in the spread of arboviral diseases. The diagnosis of these viral infections is crucial to reduce the spread and reduce disease burden. Current diagnostic tools are, however, expensive and time-consuming or lack accuracy and sensitivity. Therefore, ArboSense has the ambition to develop a detection methodology for viral RNA that will reach beyond the capabilities of the state-of-the-art in terms of specificity, sensitivity, speed and the potential for panel analysis. The novelty of the methodology lies in the combination of photoelectrochemistry, in which light is used to trigger a signal, and rolling circle amplification. This combination allows the development of a methodology that can detect a panel of three important arboviruses (i.e. Dengue, Chikungunya and Zika) simultaneously with a limit of detection in the sub-femtomolar range. Finally, the methodology will be validated on clinical serum samples. The underlying methodology can in principle be used to detect any nucleic acid sequence and, therefore, has the potential to be further extended for a wider range of applications (i.e. bacterial infections, antimicrobial resistance and cancer biomarkers).

Researcher(s)

• Promoter: De Wael Karolien
• Co-promoter: Ariën Kevin
• Fellow: Daems Elise

Research team(s)

• Antwerp engineering, PhotoElectroChemistry & Sensing (A-PECS)

Project type(s)

• Research Project

Abstract

Flaviviruses, a large group of arthropod-borne viruses transmitted by Aedes mosquito vectors in both tropical and subtropical areas, pose an increasing threat for human health. Most of the arboviral infections are either asymptomatic or present with rather mild symptoms during the acute phase. Nevertheless, a fraction of the patients develops complications with severe neurotropic illness or hemorrhagic disease in the post-acute phase. As up to 400 million people are infected with a flavivirus annually around the globe, still a considerable number of patients will evolve to more severe disease. Although for dengue virus (DENV) specifically, the vaccine Dengvaxia® was approved for use in several endemic regions, it's administration is restricted to people who experienced a prior dengue infection because of safety precautions. With other flavivirus vaccines in different stages of clinical development and also specific antiviral treatments under development, such as for example the highly potent anti-DENV compound (JNJ-64281802), there is a need for highly specific and sensitive diagnostic tools to enable correct serostatus determination and to triage patients for treatment. Although molecular diagnostic tests based on RT-qPCR have an excellent sensitivity and specificity, their application is limited to the short viremic period and to a laboratory setting that enables molecular testing. To date, the vast majority of the laboratory diagnoses relies on serology based tests, especially in low and middle income countries in endemic areas.(6) Serology is often problematic due to the high antigenic resemblance of co-circulating flaviviruses such as DENV, Zika virus (ZIKV) and yellow fever virus (YFV). In an attempt to overcome these problems, researchers at the Institute of Tropical Medicine (ITM) explored the diagnostic potential of antigenic regions at higher amino acid resolution. Several flavivirus-specific peptides as well as cross-reactive peptides were identified during microarray screenings and confirmed in bead-based multiplex immunoassays, showing a promising improvement compared to the performance of current commercial serological tests for DENV. Starting from the earlier identified peptides for DENV1-4, and based on the expertise and experience of Janssen in biomarker development, we aim to identify peptides for ZIKV and YFV in new microarray screenings, and strive to optimize DENV, ZIKV and YFV peptide biomarkers for diagnostic test development, by detailed epitope identification, by mapping virus-specific and cross-reactive epitopes, and by evaluating single- and multiple epitope-peptide hits in multiplex immunoassays. We aim to convert our findings into applicable immunological test format such as peptide ELISA's and ultimately lateral flow assay (LFAs) that allow to discriminate between DENV serotypes, ZIKV and YFV, as well as employ broadly recognized epitopes (for PanDenv and PanFlavi applications). Finally, we aim to evaluate the prototype diagnostic assay (ELISA or LFA) in a reference setting such as the ITM in Antwerp and in endemic settings in Peru and in the Democratic Republic Congo (DRC).

Researcher(s)

• Promoter: Ariën Kevin

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

InnoPath proposes an innovative technology using low-cost, accurate, rapid, easy-to-use and robust attributes of singlet oxygen based photoelectrochemistry to offer more precise, sensitive and affordable diagnostics in lab and point-of-care settings. Benchmarked against gold standard real time polymerase chain reaction (PCR), the technology will be validated for pathogen detection using patient samples. A similar point-of-care or syndromic technology for common pathogens causing acute tropical fever, with comparable or better sensitivity than PCR and cost similar to existing rapid diagnostic tests, is not available today. InnoPath aims to improve patient care and reduce the impact of infectious diseases. Furthermore, it could advance epidemiological surveillance, timely detection of outbreaks and implementation of control measures. This project aims to 1) deliver a proof-of-concept for the photoelectrochemical detection of three common pathogens causing acute tropical fever and 2) demonstrate the feasibility of translating groundbreaking technology into a biosensor for pathogen detection. This project is a strategic collaboration with the Institute of Tropical Medicine Antwerp (ITM), building on a technology platform of the University of Antwerp.

Researcher(s)

• Promoter: De Wael Karolien
• Co-promoter: Ariën Kevin

Research team(s)

• Antwerp engineering, PhotoElectroChemistry & Sensing (A-PECS)

Project type(s)

• Research Project