By Sharon Reynolds, National Institutes of Health
As the global pandemic caused by the coronavirus SARS-CoV-2 continues, researchers are working at unprecedented speed to produce new treatments and vaccines. Much work has focused on studying antibodies from the blood of people who have recovered from COVID-19, the disease caused by SARS-CoV-2.
Antibodies are molecules that are produced by the immune system to fight infection. Some research teams are testing whether antibodies against SARS-CoV-2 could be isolated and given as a treatment to others who are infected. Others are studying the structure and function of different antibodies to help guide the development of vaccines.
SARS-CoV-2 particles have proteins called spikes protruding from their surfaces. These spikes latch onto human cells, then undergo a structural change that allows the viral membrane to fuse with the cell membrane. The viral genes then enter the host cell to be copied and produce more viruses.
Several potential vaccines now under development are designed to trigger the human body to produce antibodies to the SARS-CoV-2 spike protein. Antibodies that recognize and bind to the spike protein will hopefully block the virus from infecting human cells.
To better understand antibodies against the spike protein that are naturally produced after an infection, a team led by Drs. Davide Robbiani and Michel Nussenzweig at the Rockefeller University studied 149 people who had recovered from COVID-19 and volunteered to donate their blood plasma. The participants had started experiencing symptoms of the virus an average of 39 days before sample collection.
The study was funded in part by NIH’s National Institute of Allergy and Infectious Diseases (NIAID). Results were published on June 18, 2020, in Nature.
The researchers first isolated antibodies that could bind to the receptor binding domain (RBD), a crucial region on the virus’s spike protein. They then tested whether the antibodies could neutralize SARS-CoV-2—that is, bind to the virus and stop infection.
Most participants had low or very low levels of antibodies against SARS-CoV-2. Only 1% of the study participants had high levels of antibodies that could neutralize the virus.
To examine the range of antibodies made, the researchers isolated the cells that produce antibodies—memory B cells—from the plasma of six selected participants with very high to moderate levels of neutralizing antibodies. Even in those with modest neutralizing activity in their plasma, the team found potent antibodies against the SARS-CoV-2 RBD. Surprisingly, neutralizing antibodies from different people showed remarkable similarity.
Further analysis showed that the neutralizing antibodies fell into three groups, each binding to a different part of the RBD. Together, these insights could help guide the design of vaccines or antibodies as potential treatments for COVID-19.
“We now know what an effective antibody looks like and we have found similar ones in more than one person,” Robbiani says. “This is important information for people who are designing and testing vaccines. If they see their vaccine can elicit these antibodies, they know they are on the right track.”