CoVAT - Development and Deployment of Lateral Flow Antigen Test for COVID-19

Abstract: COVID-19 is a newly emerged infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that continues to pose serious threat to global health, devastating world economy and lifestyles. Testing has been recognised as a key step in mitigation of spread of the disease since it allows for prompt clinical and well-tuned public health interventions including physical distancing measures. The current predominant testing strategy is based on the detection of SARS-CoV-2 from nasopharyngeal and/or oropharyngeal specimen by reverse transcription polymerase chain reaction (RT-PCR). Although RT-PCR is highly sensitive, it is expensive, requires skilled manpower, equipment and has a long turnaround time of up-to 24 hours. This has greatly restricted its large-scale deployment especially in low- and middle-income countries (LMICs) including Kenya. Similarly, lately developed serological tests for COVID-19 have been observed to have low sensitivity and specificity, reducing their utility. Moreover, they provide information on historical infection which may not be clinically useful. Thus, antigen-based tests for SARS-CoV-2 offer an attractive alternative solution to testing needs and possibly the only viable solution for most LMICs. Lateral Flow Antigen (LFA) tests in particular are suitably inexpensive, can be rapidly mass-produced, are easy to use, return results in minutes, and crucially, like RT-PCR and unlike serological tests, can reveal an active infection. As of July 19th, 2020, only two antigen tests had received emergency use authorization. These authorized assays require instrumentation and are not available at low cost or outside health care settings. Hence, to address these diagnostic challenges, we propose to develop an LFA test for COVID-19 that will be affordable, easy to use and does not need skilled personnel, expensive reagents nor machines. Since sufficiently accurate performance of an LFA test requires highly optimized antibodies and assay conditions, we shall leverage on an innovative high-throughput eukaryotic wheat germ cell free system to generate 5 COVID-19 antigens derived from locally circulating SARS-CoV-2 sequences. We shall then use these antigens to produce monoclonal antibodies in mice and the most efficient capture and detector pairs of antigen specific antibodies will be mounted on lateral flow strips for rapid point-of-care diagnostic test. We shall then evaluate the implementation outcomes- feasibility, acceptance, and cost effectiveness and user friendliness- of the LFA point-of-care test to inform adaptation and future scale up.