Washington University in St. Louis

COVID-19 dual-antibody therapies effective against variants in animal study

Combination therapies appear to prevent emergence of drug resistance

Newswise — COVID-19 therapies made from antibodies often are given to patients who are at high risk of severe illness and hospitalization. However, there have been nagging questions about whether such antibody therapies retain their effectiveness as worrisome new virus variants arise.

New research at Washington University School of Medicine in St. Louis suggests that many, but not all, therapies made from combinations of two antibodies are effective against a wide range of variants of the virus. Further, combination therapies appear to prevent the emergence of drug resistance.

The study, in mice and hamsters, tested all single and combination antibody-based therapies authorized for emergency use by the Food and Drug Administration (FDA), or that are being evaluated in late-stage clinical trials, against a panel of emerging international and U.S. variants of SARS-CoV-2, the virus that causes COVID-19.

The findings, published June 21 in the journal Nature, 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 — indicate that one of the two antibodies has lost some or all ability to neutralize the variant.

“We knew how these antibodies were behaving in vitro, but we don’t give people drugs based solely on cell culture data,” said senior author Michael S. Diamond, MD, PhD, the Herbert S. Gasser Professor of Medicine. “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. We’re going to have to continue to monitor the effectiveness of antibody therapy as more variants arise, but combination therapy is likely needed for treating infections with this virus as more variants emerge.”

So-called monoclonal antibodies mimic those 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. At the time this study began, there were two dual-antibody combination therapies and a single antibody therapy authorized by the FDA for emergency use. The FDA withdrew authorization for the single antibody therapy, bamlanivimab, in April on the grounds that it was not effective against the variants circulating at that time. In May, the FDA authorized the single antibody sotrovimab as a treatment for COVID-19.

In all, the researchers evaluated antibodies corresponding to the FDA-authorized ones made by Eli Lilly and Co., Regeneron and Vir Biotechnology/GlaxoSmithKline, as well as the antibodies currently under development by AbbVie, Vir and AstraZeneca that are in clinical trials.

The researchers — led by co-first authors Rita E. Chen, an MD/PhD student, Emma S. Winkler, an MD/PhD student, and Brett Case, PhD, a postdoctoral researcher — 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 (first identified in the United Kingdom), Beta (South Africa) and Gamma (Brazil) — as well as an emerging variant from India similar to the Delta variant of concern. They also tested variants from New York and California. The researchers used a mix of virus samples originally obtained from people with COVID-19 and laboratory strains genetically engineered to contain key mutations.

The researchers 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. The researchers 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 co-author Jacco Boon, PhD, an associate professor of medicine, of molecular microbiology and of pathology & immunology. “Resistance arose with some of the monotherapies, but never with combination therapy.”

Since antibody-based COVID-19 therapies primarily are used to treat people who already are infected, the researchers also evaluated how well the antibody combinations performed when given after infection with the Beta variant. The Beta variant was chosen because it has been shown to be most likely to escape neutralization in laboratory-based experiments and has the most resistance to COVID-19 vaccines. The antibody cocktails corresponding to those from AstraZeneca, Regeneron and Vir were all effective at reducing disease caused by the Gamma variant; the one from AbbVie only was partially protective, and the one from Lilly showed no efficacy at all.

“It’s going to be useful going forward to understand how these monoclonal antibodies are going to behave as variants continue to emerge,” said Diamond, who also is a professor of molecular microbiology and of pathology & immunology. “We need to think about and generate combinations of antibodies to preserve our ability to treat this disease. And we’ll need to monitor for resistance — although, in my opinion, the use of specific combinations will make this less of an issue.”

Chen RE, Winkler ES, Case JB, Aziati ID, Bricker TL, Joshi A, Darling T, Ying B, Errico JM, Shrihari S, VanBlargan LA, Xie X, Gilchuk P, Zost SJ, Droit L, Liu Z, Stumpf S, Wang D, Handley SA, Stine WB, Shi P-Y, Davis-Gardner ME, Suthar MS, Knight MG, Andino R, Chiu CY, Ellebedy AH, Fremont DH, Whelan SPJ, Crowe JE, Purcell L, Corti D, Boon ACM, Diamond MS. In vivo monoclonal antibody efficacy against SARS-CoV-2 variant strains. Nature. June 21, 2021. DOI: 10.1038/s41586-021-03720-y

MEDIA CONTACT
Register for reporter access to contact details
CITATIONS

Nature, June-2021; R01 AI157155; U01 AI151810; U01 AI141990; R01 AI118938; 75N93019C00051; HHSN272201400006C; HHSN272201400008C; HHSN75N93019C00074; PDII2018702; HR0011-18-2-0001



Filters close

Showing results

110 of 6054
access_time Embargo lifts in 2 days
Embargo will expire: 26-Jul-2021 11:00 AM EDT Released to reporters: 23-Jul-2021 5:05 PM EDT

A reporter's PressPass is required to access this story until the embargo expires on 26-Jul-2021 11:00 AM EDT The Newswise PressPass gives verified journalists access to embargoed stories. Please log in to complete a presspass application. If you have not yet registered, please Register. When you fill out the registration form, please identify yourself as a reporter in order to advance to the presspass application form.

Newswise: NIH Chooses University of Miami Miller School of Medicine to Head Project for Its Safe Return to In-Person School Initiative
Released: 23-Jul-2021 12:15 PM EDT
NIH Chooses University of Miami Miller School of Medicine to Head Project for Its Safe Return to In-Person School Initiative
University of Miami Health System, Miller School of Medicine

The University of Miami Miller School of Medicine is helping to lead a National Institutes of Health (NIH) COVID-19 testing initiative to safely return children to in-person school.

Released: 23-Jul-2021 11:40 AM EDT
New 'Atlas' Charts How Antibodies Attack Spike Protein Variants
Brigham and Women’s Hospital

As the SARS-CoV-2 virus that causes COVID-19 continues to evolve, immunologists and infectious diseases experts are eager to know whether new variants are resistant to the human antibodies that recognized initial versions of the virus.

23-Jul-2021 8:55 AM EDT
COVID Variants and a Surge Among the Unvaccinated: Live Expert Panel for July 23rd, 2021
Newswise

Panelists will discuss the threat posed by new COVID variants and continued vaccine hesitancy.

Released: 22-Jul-2021 4:05 PM EDT
COVID-19: Patients with Malnutrition May Be More Likely to Have Severe Outcomes
Scientific Reports

Adults and children with COVID-19 who have a history of malnutrition may have an increased likelihood of death and the need for mechanical ventilation, according to a study published in Scientific Reports.

access_time Embargo lifts in 2 days
Embargo will expire: 27-Jul-2021 4:05 PM EDT Released to reporters: 22-Jul-2021 3:05 PM EDT

A reporter's PressPass is required to access this story until the embargo expires on 27-Jul-2021 4:05 PM EDT The Newswise PressPass gives verified journalists access to embargoed stories. Please log in to complete a presspass application. If you have not yet registered, please Register. When you fill out the registration form, please identify yourself as a reporter in order to advance to the presspass application form.

access_time Embargo lifts in 2 days
Embargo will expire: 26-Jul-2021 4:05 PM EDT Released to reporters: 22-Jul-2021 2:45 PM EDT

A reporter's PressPass is required to access this story until the embargo expires on 26-Jul-2021 4:05 PM EDT The Newswise PressPass gives verified journalists access to embargoed stories. Please log in to complete a presspass application. If you have not yet registered, please Register. When you fill out the registration form, please identify yourself as a reporter in order to advance to the presspass application form.

Released: 22-Jul-2021 2:35 PM EDT
New Insights Into Uncontrolled Inflammation in COVID-19 Patients
Queen Mary University of London

In a new study, published recently in the journal Circulation Research, scientists discover how the production of protective molecules known as specialised pro-resolving mediators (SPM) is altered in patients with COVID-19.

Released: 22-Jul-2021 2:30 PM EDT
度假旅行者需要了解的COVID-19相关信息
Mayo Clinic

许多人会利用国家法定假日出门旅行或举办聚会。由于仍有许多人需要接种COVID-19疫苗以及传染性更强的Delta变种疫苗,因此健康专家建议,如果您计划旅行或召集很多人聚会,请务必谨慎。


Showing results

110 of 6054

close
1.25973