A healthcare worker takes a sample at a New York State Department of Health COVID-19 antibody testing center at Steve's 9th Street Market in Brooklyn, New York, the United States, on April 25, 2020. (Photo by Michael Nagle/Xinhua)
A study posted on the website of Washington University School of Medicine in St. Louis on Wednesday shows that antibody effector functions are a crucial part of effectively treating infections with SARS-CoV-2, the virus that causes COVID-19, but are dispensable when the antibodies are used to prevent infection.
To determine the role of antibody effector functions in COVID-19, the researchers started with an antibody that is very effective at recognizing and neutralizing SARS-CoV-2. They eliminated the antibody's effector functions by mutating its long arm so that it could not stimulate immune cells.
The researchers gave separate groups of mice the original or the mutated SARS-CoV-2 antibodies, or a placebo antibody that does not recognize SARS-CoV-2. The antibodies were given to the animals one day before they were infected through the nose with the virus that causes COVID-19. Regardless of whether the effector functions of the antibodies were intact, the SARS-CoV-2 antibodies protected the mice against disease. Mice that had received either of the SARS-CoV-2 antibodies lost less weight and had lower levels of virus in their lungs than the ones that received the placebo antibody. Importantly, there was no sign of antibody-dependent enhancement of disease.
The researchers then investigated whether antibody effector functions are needed for treatment after infection. They gave mice the virus that causes COVID-19 and treated them one, two or three days later with the original or mutated SARS-CoV-2 antibodies, or a placebo antibody. Compared to the placebo, the original SARS-CoV-2 antibody protected mice against weight loss and death, but the one without effector functions did not.
Further experiments with different antibodies with and without effector functions, and in a different animal, hamsters, yielded the same result: Effector functions are an indispensable part of effective antibody treatment for COVID-19.
Some antibody-based drugs for COVID-19 are being developed as preventives for use in high-risk environments such as nursing homes. But most such drugs are geared toward treating people who are already infected. For that purpose, optimizing antibody effector functions could be the key to making a powerful drug.
As part of this study, the researchers also discovered that the loss of effector functions changed the kinds of immune cells that were recruited to fight the infection and how they behaved.
The findings have been published online in the journal Cell.
