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Combination antibody therapies should retain effectiveness against emerging COVID-19 variants: study

Jun. 22, 2021, 7:39 AM

Five monoclonal antibody “cocktails,” including one developed at Vanderbilt University Medical Center (VUMC), are protective in animal studies against several variant strains of COVID-19, according to a report this week in the journal Nature.

The findings suggest that many of the combination antibody therapies currently being tested in humans should retain their effectiveness against emerging variants of the COVID-19 virus, SARS-CoV-2, the report concluded.

Although COVID-19 vaccines have begun to bring the global pandemic under control, people who are immunocompromised and cannot mount an adequate immune response due to cancer treatments or other medical conditions are not good candidates for vaccination.

“Antibodies will fill the gap for these high-risk individuals and for the unvaccinated,” said James Crowe Jr., MD, director of the Vanderbilt Vaccine Center, whose team discovered one of the monoclonal antibody cocktails described in the Nature paper.

Crowe holds the Ann Scott Carell Chair and is Professor in Pediatrics and Pathology, Microbiology & Immunology at VUMC. During the past 25 years, he and his colleagues have pioneered techniques for isolating human “monoclonal” antibodies that can neutralize a host of pathogenic viruses with a laser-like focus.

Two long-acting, neutralizing antibodies against SARS-CoV-2 discovered in the Crowe lab were optimized by the global biopharmaceutical company AstraZeneca and have been tested in phase 2/3 clinical trials as a combination investigational therapy called AZD7442. Results have not yet been reported.

Michael Diamond, MD, PhD, a leading expert in viral pathogenesis at Washington University School of Medicine in St. Louis, Missouri, is corresponding author of the Nature paper. The multi-center study also described the efficacy of monoclonal antibody cocktails developed by Regeneron Pharmaceuticals, Vir Biotechnology, AbbVie and Eli Lilly & Company.

The cocktails protected mice and hamsters from weight loss and acute illness caused by variants first identified in the United Kingdom (B.1.1.7), South Africa (B.1.351) and Brazil (B.1.1.28), while significant weight loss occurred in animals given only one antibody (monotherapy).

Treatment with only one antibody can lead to resistance, in part because of rapid selection of “escape mutations” by the virus. Resistance did not develop and no escape mutants were detected when the animals were treated with antibody cocktails.

These findings highlight the importance of using multiple monoclonal antibodies that recognize different epitopes or parts of the virus, the researchers concluded.

Others from the Vanderbilt Vaccine Center who contributed to the study were Pavlo Gilchuk, PhD, senior staff scientist, and Seth Zost, PhD, research fellow.

The study was supported in part by grants and contracts from the National Institutes of Health, the Defense Advanced Research Project Agency (DARPA), the Dolly Parton COVID-19 Research Fund at Vanderbilt, the Mercatus Center “Fast Grants” program at George Mason University, and the Merck KGaA Future Insight Prize.



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