June 2021 ESRFnews6

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We are currently seeking pharma partners to expedite the development of these antibodies into clinic

The automated MASSIF-1 beamline, run jointly by the ESRF and EMBL, has helped scientists test a new approach for identifying antibodies for SARS-CoV-2, the virus at the centre of the COVID-19 pandemic. The approach has already turned up promising therapeutic candidates, and could be used to tackle future viruses. There are currently at least 25

experimental antibodies for the neutralisation of SARS-CoV-2 undergoing clinical trials, of which two have been demonstrated in phase-3 trials to reduce hospitalisation and deaths by 70% in non-hospitalised patients. The majority of these experimental antibodies have been identified by screening a finite number in the thousands of antibody- producing white blood cells from patients who have recovered from COVID-19 specifically COVID-19 caused by the original SARS-CoV-2 strain first identified in Wuhan, China. However, the virus has since

Coronavirus-variant antibodies tested mutated into substantially different variants, potentially rendering some of the clinical candidates ineffective. A collaboration among eight

different companies, charities and academic institutions in the UK and France, formed by the UK BioIndustry Association, has worked on a different, complementary approach. It is based on phage display, a technology that involves combining antibody genes on a strand of DNA packaged in a safe viral protein, to make a phage antibody. Taking different antibody genes from COVID-19 patients, the collaboration s researchers created a library of tens of millions of phage antibodies, from which they could isolate potential neutralising molecules using SARS-CoV-2 target molecules as bait. This comprehensive search of antibody sequence space allowed the researchers to identify a diverse pool of neutralising antibodies, including ones with distinct modes of action that reduce

the likelihood of escape of SARS- CoV-2 variants. The authors of the latest study went

to the ESRF and used the MASSIF-1 beamline to determine the mechanisms by which some of their phage-derived antibodies neutralised SARS-CoV-2. The synchrotron data also allowed them to predict the potential of the antibodies against emerging viral variants, which was later confirmed in virus neutralisation assays at the UK government s National Institute for Biological Standards and Control (Front. Immunol. in press). We are currently seeking pharma

partners to expedite the development of these antibodies into clinic, says Aneesh Karatt-Vellatt, the lead author of the study who is based at the biotech company IONTAS in Cambridge, UK. Beyond the immediate therapeutic prospect, the rigorous and multifaceted approach used for this study provides a template for antibody discovery in future pandemics.

MASSIF-1 tests antibodies delivered by phage display technology for SARS-CoV-2.