Potent antibodies found in people recovered from COVID-19 | National Institutes of Health (NIH)

Potent antibodies found in people recovered from COVID-19 | National Institutes of Health (NIH)

Potent antibodies found in people recovered from COVID-19

At a Glance

• Although most people who recovered from COVID-19 had low levels of antibodies to SARS-CoV-2 in their blood, researchers identified potent infection-blocking antibodies.
• Their careful analysis of the antibodies may provide guidance for developing vaccines and antibodies as treatments for COVID-19.

Colorized scanning electron micrograph of a cell (red), isolated from a patient sample, that is heavily infected with SARS-COV-2 virus particles (yellow). NIAID Integrated Research Facility

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.

Three neutralizing antibodies (blue, purple and orange) bound to the receptor binding domain on the SARS-CoV-2 spike proteinChristopher O. Barnes and Pamela J. Bjorkman, California Institute of Technology

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.”

—by Sharon Reynolds

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References: Convergent antibody responses to SARS-CoV-2 in convalescent individuals. Robbiani DF, Gaebler C, Muecksch F, Lorenzi JCC, Wang Z, Cho A, Agudelo M, Barnes CO, Gazumyan A, Finkin S, Hägglöf T, Oliveira TY, Viant C, Hurley A, Hoffmann HH, Millard KG, Kost RG, Cipolla M, Gordon K, Bianchini F, Chen ST, Ramos V, Patel R, Dizon J, Shimeliovich I, Mendoza P, Hartweger H, Nogueira L, Pack M, Horowitz J, Schmidt F, Weisblum Y, Michailidis E, Ashbrook AW, Waltari E, Pak JE, Huey-Tubman KE, Koranda N, Hoffman PR, West AP Jr, Rice CM, Hatziioannou T, Bjorkman PJ, Bieniasz PD, Caskey M, Nussenzweig MC. Nature. 2020 Jun 18. doi: 10.1038/s41586-020-2456-9. Online ahead of print. PMID: 32555388.

Funding: NIH’s National Institute of Allergy and Infectious Diseases (NIAID) and National Center for Advancing Translational Sciences (NCATS); Caltech Merkin Institute for Translational Research; George Mason University; European ATAC Consortium; G. Harold and Leila Y. Mathers Charitable Foundation; Robert S. Wennett Post-Doctoral Fellowship; Shapiro-Silverberg Fund for the Advancement of Translational Research; Howard Hughes Medical Institute.