Dual-antibody therapy effective against COVID variants in animal study
Washington, Jun 22: COVID-19 therapies made from a cocktail of two types of antibodies were found to be effective against a wide range of variants of the coronavirus in a study on mice and hamsters, scientists say.
The researchers tested single and combination antibody therapies authorised for emergency use by the Food and Drug Administration (FDA), or that are in late-stage clinical trials, against emerging variants of SARS-CoV-2, the virus that causes COVID-19.
The study, published on Monday in the journal Nature, suggests that many, but not all, therapies made from combinations of two antibodies are effective against a wide range of variants of the virus in mice and hamsters.
The researchers from the Washington University School of Medicine in St. Louis in the US also found that combination therapies appear to prevent the emergence of drug resistance.
The findings suggest that COVID-19 drugs made of two antibodies often retain potency as a therapy against variants even when in vitro studies -- experiments conducted in a dish.
"We knew how these antibodies were behaving in vitro, but we don''t give people drugs based solely on cell culture data," said study senior author Michael S Diamond, a professor of Medicine at Washington University.
"When we looked in animals, there were some surprises. Some of the combinations performed better than we thought they would, based on in vitro data. And there was no drug resistance to combinations whatsoever, across all of the different variants," Diamond said.
The researchers said the effectiveness of antibody therapy should be monitored as more variants arise. However, they noted a combination therapy is likely needed for treating infections with this virus as more variants emerge.
Monoclonal antibodies mimic natural antibodies generated by the body to fight off the virus that causes COVID-19. Administration of antibody therapies bypasses the body''s slower and sometimes less effective process of making its own antibodies.
The researchers tested the antibodies against a panel of virus variants containing key mutations in their spike genes. The SARS-CoV-2 virus uses spike protein to invade cells.
All monoclonal antibody-based COVID-19 therapies work by interfering with the interaction between spike protein and cells.
The panel included mutations found in three of the four variants that have been designated "variants of concern" by the World Health Organization -- Alpha, Beta, Gamma as well as an emerging variant from India similar to the Delta strain.
They also tested variants from New York and California in the US.
The team used a mix of virus samples originally obtained from people with COVID-19 and laboratory strains genetically engineered to contain key mutations.
They evaluated the antibodies in hamsters and two strains of mice.
The researchers first gave the animals antibodies -- singly or in the same combinations in which they are given to treat patients -- a day before infecting them with one of the virus variants.
They monitored the animals'' weight for six days and then measured the amount of virus in their noses, lungs and other parts of the body.
Although some single antibodies showed reduced or no ability to neutralize virus variants in a dish, low doses of most of the antibody combinations protected against disease caused by many of the variants.
The researchers sequenced viral samples from the animals and found no evidence of drug resistance in viruses from any of the animals that had been treated with combination therapies.
"Dual therapy seemed to prevent the emergence of resistant viruses," said study co-author Jacco Boon, an associate professor of medicine.
"Resistance arose with some of the monotherapies, but never with combination therapy," Boon added.