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Antibody Clears Covid-19 Variants, Enters Trial

SARS-Cov-2 virus

Scanning electron microscope image of SARS-Cov-2 virus, responsible for Covid-19 infections (NIH.gov)

4 May 2021. A synthetic antibody is shown in lab tests to neutralize variants of the SARS-CoV-2 virus, and will be added to an ongoing clinical trial of Covid-19 therapies. The antibody, developed by AbCellera Biologics Inc. in Vancouver, British Columbia, is code-named LY-CoV1404, as part of the company’s continuing collaboration with drug maker Eli Lilly and Company in Indianapolis.

AbCellera says it designed LY-CoV1404 to bind to the spike protein on the surface of SARS-CoV-2 viruses, like other Covid-19 therapies. However, the antibody is also configured to target specific mutating amino acids associated with SARS-CoV-2 variants in the receptor binding domain of the spike protein’s chemistry. As a result, says the company, LY-CoV1404 antibodies can neutralize many of the known emerging viral variants.

In lab tests posted yesterday on the BioRxiv preprint server, researchers from AbCellera, Eli Lilly, and other labs in the U.S. and Canada reported test results on a blood sample from a Covid-19 patient, 60 days following infection. The team tested LY-CoV1404 on analogues of the B.1.1.7 (U.K.), B.1.351 (South Africa), P.1 (Brazil), B.1.426/B.1.429 (California), and B.1.526 (New York) viral variants added to the sample, and found the synthetic antibody neutralized all of them. The paper is posted by the authors, and the findings are not yet peer reviewed.

AbCellera uses what it calls deep mining of B-cells from the immune system to discover antibodies for preventing and treating diseases caused by a range of viruses and bacteria. B-cells are white blood cells in the immune system that produce antibodies, proteins that directly attack invading pathogens, such as bacteria, viruses, and parasites. The company’s antibody discovery process combines a number of technologies, beginning with single-cell screening with microfluidics, or lab-on-a-chip devices. AbCellera also uses advanced bioinformatics and artificial intelligence for further analysis and high-throughput characterization to express hundreds of antibodies.

Adding antibody to current clinical trial

In March 2020, AbCellera began a collaboration with Eli Lilly to develop Covid-19 therapies, which led to the synthetic antibody bamlanivimab. In February of this year, as reported in Science & Enterprise, Food and Drug Administration authorized bamlanivimab combined with another Eli Lilly antibody etesevimab to treat people with Covid-19 infections showing mild to moderate symptoms, but considered at high risk for severe symptoms of the disease.

FDA based the emergency authorization in part on results from a mid-stage clinical trial testing the antibodies on their own and in combination, including cocktails with treatments from other developers. AbCellera and Eli Lilly plan to add LY-CoV1404 to the same trial, testing the antibody among non-hospitalized patients with mild to moderate symptoms on its own and combined with other antibodies.

In addition, says AbCellera, the potency of LY-CoV1404 suggests it can be given in lower doses as a subcutaneous or under-the-skin injection, making it simpler to administer than infusions. “LY-CoV1404’s powerful neutralization of SARS-CoV-2 allows for exploration of lower clinical doses, which may support subcutaneous administration and availability of more doses to treat patients around the world,” says Bo Barnhart, AbCellera’s scientific director in a company statement.

Barnhart, also senior author of the preprint paper adds, “The ability of SARS-CoV-2 variants to negatively alter the trajectory of the pandemic emphasizes the essential need for antibody therapies that can be developed in real time to combat the virus as it evolves.”

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