Antibodies vary widely in their efficacy. While many may latch on to the virus, only some are truly “neutralizing,” meaning that they actually block the virus from entering the cells. Image is in the public domain.
First results from human COVID-19 immunology study reveal universally effective antibodies
Summary: While the amount of antibodies generated varies widely in patients who have recovered from coronavirus, most people generate at least some antibodies which are intrinsically capable of neutralizing the SARS-CoV-2 virus.
Source: Rockerfeller University
The first round of results from an immunological study of 149 people who have recovered from COVID-19 show that although the amount of antibodies they generated varies widely, most individuals had generated at least some that were intrinsically capable of neutralizing the SARS-CoV-2 virus.
Antibodies vary widely in their efficacy. While many may latch on to the virus, only some are truly “neutralizing,” meaning that they actually block the virus from entering the cells.
Since April 1, a team of immunologists, medical scientists, and virologists, has been collecting blood samples from volunteers who have recovered from COVID-19. The majority of the samples they have studied showed poor to modest “neutralizing activity,” indicating a weak antibody response. However, a closer look revealed everyone’s immune system is capable of generating effective antibodies—just not necessarily enough of them. Even when neutralizing antibodies were not present in an individual’s serum in large quantities, researchers could find some rare immune cells that make them.
“This suggests just about everybody can do this, which is very good news for vaccines,” says Michel C. Nussenzweig, head of the Laboratory of Molecular Immunology at Rockefeller. “It means if you were able to create a vaccine that elicits these particular antibodies, then the vaccine is likely to be effective and work for a lot of people.”
Moreover, the researchers identified three distinct antibodies that were shown to be the most potent of the bunch in neutralizing the virus. They are working to develop them further into therapeutic and preventive drugs.
The findings are shared on BioRxiv ahead of submission to peer-reviewed scientific journals. Nussenzweig’s collaborators include, Davide F. Robbiani, Marina Caskey, Paul Bieniasz, Theodora Hatziioannou, and Charles M. Rice.
From the beginning of April and over 5 weeks, 149 people who had recovered from COVID-19 visited The Rockefeller Hospital to donate plasma, the portion of the blood that contains the antibodies, and the immune B-cells that produce them. The participants had experienced symptoms for an average of 12 days, and had their first symptoms on average 39 days before plasma donation.
Bieniasz and Hatziioannou’s team used an essay they had developed to test the neutralizing activity of the plasma samples. This involved mixing the plasma with a pseudo SARS-CoV-2 virus and measuring how well this mixture could still infect human cells in a dish.
In 33 percent of donors, the neutralizing activity of plasma was below detectable levels. It’s possible that for many in this group, their immune system’s first line of defense had resolved the infection quickly, before the antibody-producing cells were called in.
The majority of the plasma samples showed poor to modest neutralizing activity. And for 1 percent of donors it was remarkably high. “Like in other diseases, everyone responds differently,” says Robbiani, research associate professor at Laboratory of Molecular Immunology. “Some people have poor response, some average. And then there is a fraction of people that are exceptional responders.”
Those “elite” responders are crucial to the team’s plans. The high numbers of neutralizing antibodies in their serum makes it possible for researcher to catch the rare B cells that make them. They can then clone the antibodies from those cells, and use them to emulate the same strong defense in other people.
Out of the numerous antibodies generated by elite responders who had the best performing plasma, the team identified 40 that neutralized the virus, and zeroed in on three that could do so even at very low concentrations. The team has cloned these most potent antibodies and is now working to develop them for clinical use.
Neutralizing antibodies found in this study bind to at least three distinct sites on the receptor-binding domain (RBD) subunit of the spike protein, which is what SARS-CoV-2 uses to gain entry to host cells. A second look at the low-performing plasma samples revealed they also contained these RBD-binding antibodies, albeit in small quantities.
“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.”
Source: Rockerfeller University Media Contacts: Katherine Fenz – Rockerfeller University Image Source: The image is in the public domain.
Original Research: Closed access “Convergent Antibody Responses to SARS-CoV-2 Infection in Convalescent Individuals”. by Davide F. Robbiani, Christian Gaebler, Frauke Muecksch, Julio C. C. Lorenzi, Zijun Wang, Alice Cho, Marianna Agudelo, Christopher O. Barnes, Anna Gazumyan, Shlomo Finkin, Thomas Hagglof, Thiago Y. Oliveira, Charlotte Viant, Arlene Hurley, Hans-Heinrich Hoffmann, Katrina G. Millard, Rhonda G. Kost, Melissa Cipolla, Kristie Gordon, Filippo Bianchini, Spencer T. Chen, Victor Ramos, Roshni Patel, Juan Dizon, Irina Shimeliovich, Pilar Mendoza, Harald Hartweger, Lilian Nogueira, Maggi Pack, Jill Horowitz, Fabian Schmidt, Yiska Weisblum, Eleftherios Michailidis, Alison W. Ashbrook, Eric Waltari, John E. Pak, Kathryn E. Huey-Tubman, Nicholas Koranda, Pauline R. Hoffman, Anthony P. West Jr., Charles M. Rice, Theodora Hatziioannou, Pamela J. Bjorkman, Paul D. Bieniasz, Marina Caskey, Michel C. Nussenzweig. BioRxiv doi:10.1101/2020.05.13.092619
Convergent Antibody Responses to SARS-CoV-2 Infection in Convalescent Individuals
During the COVID-19 pandemic, SARS-CoV-2 infected millions of people and claimed hundreds of thousands of lives. Virus entry into cells depends on the receptor binding domain (RBD) of the SARS-CoV-2 spike protein (S). Although there is no vaccine, it is likely that antibodies will be essential for protection. However, little is known about the human antibody response to SARS-CoV-21–5. Here we report on 149 COVID-19 convalescent individuals. Plasmas collected an average of 39 days after the onset of symptoms had variable half-maximal neutralizing titers ranging from undetectable in 33% to below 1:1000 in 79%, while only 1% showed titers >1:5000. Antibody cloning revealed expanded clones of RBD-specific memory B cells expressing closely related antibodies in different individuals. Despite low plasma titers, antibodies to three distinct epitopes on RBD neutralized at half-maximal inhibitory concentrations (IC50s) as low as single digit ng/mL. Thus, most convalescent plasmas obtained from individuals who recover from COVID-19 do not contain high levels of neutralizing activity. Nevertheless, rare but recurring RBD-specific antibodies with potent antiviral activity were found in all individuals tested, suggesting that a vaccine designed to elicit such antibodies could be broadly effective.
Competing Interest Statement
In connection with this work The Rockefeller University has filed a provisional patent application on which D.F.R. and M.C.N are inventors.