Scripps Research Institute

Scientists discover key element of strong antibody response to COVID-19

The findings support many vaccine strategies being used to tackle the new coronavirus
13-Jul-2020 12:25 PM EDT, by Scripps Research Institute

Newswise — LA JOLLA, CA--A team led by scientists at Scripps Research has discovered a common molecular feature found in many of the human antibodies that neutralize SARS-CoV-2, the coronavirus that causes COVID-19.

The scientists, whose study appears July 13 in Science, reviewed data on nearly 300 anti-SARS-CoV-2 antibodies that their labs and others have found in convalescent COVID-19 patients over the past few months. They noted that a subset of these antibodies is particularly powerful at neutralizing the virus--and these potent antibodies are all encoded, in part, by the same antibody gene, IGHV3-53.

The scientists used a powerful tool known as X-ray crystallography to image two of these antibodies attached to their target site on SARS-CoV-2. The resulting atomic-structure details of this interaction should be useful to vaccine designers, as well as to scientists hoping to develop antiviral drugs targeting the same site on SARS-CoV-2.

Prior research suggests that antibodies encoded by IGHV3-53 are generally present, at least in small numbers, in healthy people's blood. The results therefore offer hope that using a vaccine to boost levels of these ever-present antibodies will protect adequately against the virus.

"This type of antibody has been isolated frequently in studies of COVID-19 patients, and we can now understand the structural basis for its interaction with SARS-CoV-2," says the study's senior author Ian Wilson, DPhil, Hansen Professor of Structural Biology and Chair of the Department of Integrative Structural and Computational Biology at Scripps Research.

"This study provides important inspiration for effective COVID-19 vaccine design," says co-author Dennis Burton, PhD, professor and co-chair of the Department of Immunology and Microbiology at Scripps Research.

The research was a collaboration chiefly involving the Wilson and Burton labs, and the Scripps Research-based Neutralizing Antibody Center of IAVI, a prominent non-profit vaccine research organization.

SARS-CoV-2 so far has infected more than 12 million people around the world and killed more than 500,000, in addition to causing widespread socioeconomic disruption and damage. Developing an effective vaccine to stop the pandemic is currently the world's top public health priority.

Although several potential vaccines are already in clinical trials, scientists don't yet have a full understanding of the molecular features that would define a protective antibody response. In the new study, the scientists took a big step toward that goal.

The team started by analyzing 294 different SARS-CoV-2-neutralizing antibodies isolated from COVID-19 patients' blood over the past few months. Antibodies are Y-shaped proteins made in immune cells called B-cells. Each B-cell makes a specific antibody type, or clone, which is encoded by a unique combination of antibody genes in the cell. The scientists found that an antibody gene called IGHV3-53 was the most common of the genes for the 294 antibodies, encoding about 10 percent of them.

The scientists also noted that the IGHV3-53-encoded antibodies in their study contain an unusually short variant of the CDR H3 loop, normally a key target-binding element. These antibodies are nevertheless very potent against SARS-CoV-2 when compared to other antibodies not encoded by IGHV3-53.

A powerful response right off the bat

The IGHV3-53 antibodies had yet another property suggesting that boosting their numbers would be a good and achievable aim for a SARS-CoV-2 vaccine: They appeared to have mutated only minimally from the original versions that would be circulating, initially in small numbers, in the blood of healthy people.

Normally, when activated by an encounter with a virus to which they fit, B-cells will start proliferating and also mutating parts of their antibody genes, in order to generate new B-cells whose antibodies fit the viral target even better. The more mutations needed for this "affinity maturation" process to generate virus-neutralizing antibodies, the harder it can be to induce this same process with a vaccine.

Fortunately, the IGHV3-53 antibodies found in the study seemed to have undergone little or no affinity maturation and yet were already very potent at neutralizing the virus--which hints that a vaccine may be able to induce a protective response from these potent neutralizers relatively easily.

"Coronaviruses have been around for hundreds to thousands of years, and one can imagine that our immune system has evolved in such a way that we carry antibodies like these that can make a powerful response right off the bat, so to speak" Wilson says.

Map for vaccine-makers, gauge for clinical trials

Wilson's team used high-resolution X-ray crystallography to image two different IGHV3-53 antibodies bound to their target on SARS-CoV-2. This target, known as the receptor binding site, is a crucial structure on the viral "spike" protein that normally connects to a receptor on human cells to begin the process of cell infection. Many of the antibodies that neutralize SARS-CoV-2 appear to do so by blocking this virus-receptor connection.

"We were able to reveal unique structural features of these IGHV3-53-encoded antibodies--features that facilitate their high binding affinity and their specificity for the SARS-CoV-2 receptor binding site," says co-first author Meng Yuan, PhD, a postdoctoral research associate in the Wilson lab.

The detailed atomic-scale structural data should be of interest to vaccine designers and drug developers. Moreover, the researchers say, the identification of IGHV3-53-encoded antibodies as key elements of the immune response to COVID-19 suggests that levels of these antibodies might be useful as an indirect marker of success in ongoing and future vaccine trials.



"Structural basis of a shared antibody response to SARS-CoV-2" was written by first authors Meng Yuan, Hejun Liu, and Nicholas Wu, all of the Wilson lab; and by Chang-Chun Lee, Xueyong Zhu, Fangzhu Zhao, Deli Huang, Wenli Yu, Yuanzi Hua, Henry Tien, Thomas Rogers, Dennis Burton, and Ian Wilson, all of Scripps Research; and Elise Landais, Devin Sok and Joseph Jardine of IAVI.

The research was supported by the National Institutes of Health (K99 AI139445, UM1 AI44462), the Bill and Melinda Gates Foundation (OPP1170236) and IAVI.


Filters close

Showing results

110 of 2927
Released: 14-Aug-2020 4:55 PM EDT
Managing your child’s diabetes during COVID-19
University of Texas Health Science Center at Houston

These days it’s hard not to worry about whether a quick outing to the grocery store will result in catching COVID-19. But for parents with children who have preexisting health conditions such as diabetes, it can be especially hard not to worry about whether their child is at a higher risk of becoming severely ill from the virus.

Newswise: 1200x800?cb=1597350935
Released: 14-Aug-2020 3:35 PM EDT
Gaiters do no harm: WVU toxicologists find coverings help contain the spread of exhaled droplets
West Virginia University

Experts with the West Virginia University Center for Inhalation Toxicology found that – assuming it’s a good fit - a gaiter will, despite recent reports, provide a respiratory containment of exhaled droplets comparable to a common over-the-ear cloth mask.

Newswise: AI software enables real-time 3D printing quality assessment
Released: 14-Aug-2020 3:05 PM EDT
AI software enables real-time 3D printing quality assessment
Oak Ridge National Laboratory

Oak Ridge National Laboratory researchers have developed artificial intelligence software for powder bed 3D printers that assesses the quality of parts in real time, without the need for expensive characterization equipment.

Newswise: Is the COVID-19 virus pathogenic because it depletes specific host microRNAs?
Released: 14-Aug-2020 3:05 PM EDT
Is the COVID-19 virus pathogenic because it depletes specific host microRNAs?
University of Alabama at Birmingham

Why is the COVID-19 virus deadly, compared to cold-causing coronaviruses? Analysis current literature and bioinformatic study of seven coronaviruses, suggests that SARS-CoV-2 acts as a microRNA “sponge,” leading to better viral replication and blockage of the host immune response.

Released: 14-Aug-2020 2:30 PM EDT
UW team developing model to help lower COVID-19 infections in Seattle, other major cities
University of Washington

A UW team has received a grant to develop a model that uses local data to generate policy recommendations that could help lower COVID-19 infections in King County, which includes Seattle.

Newswise: Cardiovascular risk factors tied to COVID-19 complications and death
12-Aug-2020 7:05 PM EDT
Cardiovascular risk factors tied to COVID-19 complications and death

COVID-19 patients with cardiovascular comorbidities or risk factors are more likely to develop cardiovascular complications while hospitalized, and more likely to die from COVID-19 infection, according to a new study published August 14, 2020 in the open-access journal PLOS ONE by Jolanda Sabatino of Universita degli Studi Magna Graecia di Catanzaro, Italy, and colleagues.

Newswise: Study shows frequently used serology test may not detect antibodies that could confirm protection against reinfection of COVID-19
Released: 14-Aug-2020 1:55 PM EDT
Study shows frequently used serology test may not detect antibodies that could confirm protection against reinfection of COVID-19
University of Texas M. D. Anderson Cancer Center

Two different types of detectable antibody responses in SARS-CoV-2 (COVID-19) tell very different stories and may indicate ways to enhance public health efforts against the disease, according to researchers at The University of Texas MD Anderson Cancer Center. Antibodies to the SARS-CoV-2 spike protein receptor binding domain (S-RBD) are speculated to neutralize virus infection, while the SARS-CoV-2 nucleocapsid protein (N-protein) antibody may often only indicate exposure to the virus, not protections against reinfection.

Released: 14-Aug-2020 1:50 PM EDT
USC scientists identify the order of COVID-19's symptoms
University of Southern California (USC)

USC researchers have found the likely order in which COVID-19 symptoms first appear: fever, cough, muscle pain, and then nausea, and/or vomiting, and diarrhea.

Released: 14-Aug-2020 1:45 PM EDT
Stay the Course with Personal Finances during Pandemic, Johns Hopkins Expert Advises
Johns Hopkins University Carey Business School

Keeping on a careful and steady path is the wisest approach to personal money management during the uncertainties of the COVID-19 crisis, says Associate Professor Yuval Bar-Or of the Johns Hopkins Carey Business School.

access_time Embargo lifts in 2 days
Embargo will expire: 17-Aug-2020 11:00 AM EDT Released to reporters: 14-Aug-2020 1:25 PM EDT

A reporter's PressPass is required to access this story until the embargo expires on 17-Aug-2020 11:00 AM EDT The Newswise PressPass gives verified journalists access to embargoed stories. Please log in to complete a presspass application. If you have not yet registered, please Register. When you fill out the registration form, please identify yourself as a reporter in order to advance to the presspass application form.

Showing results

110 of 2927