Antibody effector functions are key to combatting COVID-19, finds study
Rodent studies show that using antibodies with different targets and modes of action in combination is more effective at preventing and treating COVID-19.
Researchers have shown that the effector functions of antibodies targeting SARS-CoV-2 are more important for protecting against COVID-19 (the disease caused by the virus) than their ability to prevent SARS-CoV-2 from infecting cells. The team also observed that combinations of antibodies targeting the coronavirus in different ways were more effective at preventing and treating COVID-19 in rodent models.
Human antibodies that can neutralise SARS-CoV-2, preventing it from infecting cells, or potentially treat COVID-19 have been the focus of a lot of research during the pandemic. While several potent antibodies that bind to the Spike (S) protein on the virus’s surface have been identified, for the most part they have been tested in in vitro cell cultures. In the new paper, researchers observed how in vitro results translate to protection in animals.
In the study published in the Journal of Experimental Medicine (JEM), researchers examined the properties of highly potent human monoclonal antibodies (hu-mAbs) in two rodent models: a Syrian hamster model of SARS-CoV-2 and a mouse-adapted model of SARS-CoV-2 infection (SARS-CoV-2 MA). They found that the ability of antibodies to prevent SARS-CoV-2 infecting cells in vitro did not necessarily correlate with in vivo protection. Instead, they observed that the ability of antibodies to bind to activating Fc receptors contributed to optimal protection against SARS-CoV-2.
Research teams at the University of North Carolina at Chapel Hill and The Rockefeller University, both US, reported that certain hu-mAbs which were relatively poor at blocking viral entry into cultured cells, had a more potent protective effect than expected in the rodents. The researchers determined that this is partly because, in addition to blocking viral entry, the antibodies can activate various types of white blood cells to target the virus and/or virally infected cells.
The team also observed that certain hu-mAbs were more effective when administered in combination with each other. The researchers reported that pairs of antibodies that target slightly different parts of the SARS-CoV-2 S protein could successfully prevent or treat SARS-CoV-2 infection in mice and hamsters at much lower doses than single-antibody treatments. They added that this is a particularly attractive approach to combatting COVID-19 because targeting multiple parts of the S protein reduces the chance of the virus mutating and becoming resistant to treatment.
Timothy Sheahan, an assistant professor at the Gillings School of Public Health at the University of North Carolina at Chapel Hill, who led the research team at that institute, concluded: “Overall, our data support the idea that specific combinations of antibodies with the ability to activate immune cells should be developed for optimal protection and therapy against SARS-CoV-2.”