SOMAmer technology to diagnose coronavirus infection: veterinary and zoonotic implications

Thesis

The severe effects of the COVID-19 pandemic on human health, healthcare systems, and its social and economic impacts led to the development of the 100 Days Mission. This initiative has the ambition to respond to infectious disease threats within 100 days of recognition of a potential pandemic to ensure the supply of diagnostics, vaccines and therapeutics. A key requirement for the rapid, scalable, and affordable production of diagnostic tools is the development of molecular recognition elements (MREs) which for antigen detection are currently based on monoclonal antibodies (mAbs). Compared with mAbs, ssDNA SOMAmers offer a potential alternative for a more rapid and cost-effective solution to the 100DM challenge. Research was undertaken to evaluate a library of SOMAmers raised in 2020 against the SARS-CoV-2 Wuhan-Hu-1 strain spike protein and its subdomains. An ELONA assay was developed and used to determine the binding properties of SOMAmers with a broad range of coronaviruses, including SARS-CoV-2 variants, sarbecoviruses, and viruses from the wider alpha, beta, and gammacoronavirus genera. Individual SOMAmers displayed varying binding patterns, either species-specific against SARS-CoV-2 or across sarbecoviruses, but with limited binding responses against more diverse genera. Selected SOMAmers were evaluated using competition-based approaches to identify non-competing epitope pairs that function as capture and detection MREs. SOMAmer pairs were used in the early development of a lateral flow test as a rapid, scalable, portable mass-testing platform for the detection of viral antigens as a screening or confirmatory diagnostic. An early prototype LFT based exclusively on SOMAmers was demonstrated, and further optimisation and development would be required before full validation and field trials. Through these studies, we deepened our understanding of the potential for SOMAmers to replace mAbs in a rapid antigen diagnostic test, further work is required to determine whether SOMAmers can meet the challenges posed by the 100DM aspirations.

Authors: Chadwick, JW

• DOI: 10.5287/ora-xrga7e0yn
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Subjects: Biotechnology projects; Veterinary diagnostic virology; Virology