As We Wait for a Vaccine, Scientists Work to Scale Up the Best COVID-19 Antibodies to Give New Patients

In this illustration of immune defense, Y-shaped proteins called antibodies attack a virus.

(© Siarhei/Adobe)


When we get sick, our immune system sends its soldier cells to the battlefield. Called B-cells, they "examine" the foreign particles that shouldn't be in our bloodstream—and start producing the antibodies, the proteins to neutralize the invaders.

To screen the antibodies, scientists have developed a proprietary way to make the effective ones glow – like a literal "lightbulb" moment.

The better these antibodies are at neutralizing the pathogen, the faster we recover.

The antibodies acquired from COVID-19 survivors already showed promise in treating other patients, but because they must be obtained from people, generating a regular supply is not feasible. To close the gap, researchers are trying to identify the B-cells that make the best antibodies—and then farm them in laboratories at scale.

Scientists at Berkley Lights, a biotechnology company in California, have been screening B-cells from recovered patients and testing the antibodies they release for virus-neutralizing abilities. To screen the antibodies, scientists there have developed a proprietary way to make the effective ones glow – like a literal "lightbulb" moment.

So how does it work? First, the individual B-cells are placed into microscopic chambers called nano-pens, where they secrete the antibodies. Once released, the antibodies are flushed over tiny beads that have bits of the viral particles attached to them, along with special molecules that can emit fluorescent light.

"When an antibody binds to the bead, we see a bright light on the bead," explains John Proctor, the company's senior vice president of antibody therapeutics. "So we can identify which cells are making the antibodies."

Then the antibodies are tested for their ability to counteract the coronavirus's spike proteins, which the virus uses to break into our cells. Not all antibodies are equally good at this crucial defense move—some can block only parts of the virus's machinery, while others can neutralize it completely. Proctor and his colleagues are looking for the latter.

Once scientists identify the best performing B-cells, they crack the cells open—or in scientific terms "lyse" them—and extract the genetic instructions for making the antibodies. As it turns out, B-cells aren't very efficient at pumping out massive amounts of antibodies, so scientists insert these genetic instructions into a different, more prolific type of cell.

Named Chinese Hamster Ovary Cells or CHO, these cells are commonly used in the pharmaceutical industry because they can generate therapeutic proteins en masse. Under the right nutrient conditions, which include a lot of sugar, CHO cells can keep making the antibodies at commercial levels. "They are engineered to operate in very large bioreactors," Proctor explains.

While traditional antibody screening can take three months, the Beacon System can do it in less than 24 hours.

Berkeley Lights' technology has already been used to screen the antibodies of recovered patients from Vanderbilt University Medical Center. In another example, a biotech company GenScript ProBio used the platform to screen mice engineered to have human antibodies for the coronavirus.

In addition to its small, lab-on-a-chip size, Berkeley Lights' system allows scientists to greatly speed up the screening process. While traditional antibody screening can take three months, the Beacon System can do it in less than 24 hours. "We only need one B-cell per pen and a couple of beads to see that fluorescent signal," Proctor says. "It is a more advanced way to process and analyze cells, and that level of sensitivity is unique to our technology."

B-cells secreting antibodies inside the Berkeley Lights Beacon System Nano-Pens.

(Image Credit: the Australian Institute for Bioengineering & Nanotechnology at The University of Queensland)

While vaccines are likely to take months to develop and test, antibodies might arrive to the battleground sooner. With the extremely limited treatment options for COVID-19, antibody-based therapeutics can potentially bridge this gap.

Lina Zeldovich
Lina Zeldovich has written about science, medicine and technology for Scientific American, Reader’s Digest, Mosaic Science and other publications. She’s an alumna of Columbia University School of Journalism and the author of the upcoming book, The Other Dark Matter: The Science and Business of Turning Waste into Wealth, from Chicago University Press. You can find her on http://linazeldovich.com/ and @linazeldovich.
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Amber Freed and Maxwell near their home in Denver, Colorado.

Courtesy Amber Freed

Amber Freed felt she was the happiest mother on earth when she gave birth to twins in March 2017. But that euphoric feeling began to fade over the next few months, as she realized her son wasn't making the same developmental milestones as his sister. "I had a perfect benchmark because they were twins, and I saw that Maxwell was floppy—he didn't have muscle tone and couldn't hold his neck up," she recalls. At first doctors placated her with statements that boys sometimes develop slower than girls, but the difference was just too drastic. At 10 month old, Maxwell had never reached to grab a toy. In fact, he had never even used his hands.

Thinking that perhaps Maxwell couldn't see well, Freed took him to an ophthalmologist who was the first to confirm her worst fears. He didn't find Maxwell to have vision problems, but he thought there was something wrong with the boy's brain. He had seen similar cases before and they always turned out to be rare disorders, and always fatal. "Start preparing yourself for your child not to live," he had said.

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Lina Zeldovich
Lina Zeldovich has written about science, medicine and technology for Scientific American, Reader’s Digest, Mosaic Science and other publications. She’s an alumna of Columbia University School of Journalism and the author of the upcoming book, The Other Dark Matter: The Science and Business of Turning Waste into Wealth, from Chicago University Press. You can find her on http://linazeldovich.com/ and @linazeldovich.

On May 13th, scientific and medical experts will discuss and answer questions about the vaccine for those under 16.

Photo by Kelly Sikkema on Unsplash

This virtual event will convene leading scientific and medical experts to discuss the most pressing questions around the COVID-19 vaccines for children and teens. A public Q&A will follow the expert discussion.

DATE:

Thursday, May 13th, 2021

12:30 p.m. - 1:45 p.m. EDT

LOCATION:

Virtual on Zoom

REGISTER NOW

You can submit a question for the speakers upon registering.

Dr. H. Dele Davies, M.D., MHCM

Senior Vice Chancellor for Academic Affairs and Dean for Graduate Studies at the University of Nebraska Medical (UNMC). He is an internationally recognized expert in pediatric infectious diseases and a leader in community health.

Dr. Emily Oster, Ph.D.

Professor of Economics at Brown University. She is a best-selling author and parenting guru who has pioneered a method of assessing school safety.

Dr. Tina Q. Tan, M.D.

Professor of Pediatrics at the Feinberg School of Medicine, Northwestern University. She has been involved in several vaccine survey studies that examine the awareness, acceptance, barriers and utilization of recommended preventative vaccines.

Dr. Inci Yildirim, M.D., Ph.D., M.Sc.

Associate Professor of Pediatrics (Infectious Disease); Medical Director, Transplant Infectious Diseases at Yale School of Medicine; Associate Professor of Global Health, Yale Institute for Global Health. She is an investigator for the multi-institutional COVID-19 Prevention Network's (CoVPN) Moderna mRNA-1273 clinical trial for children 6 months to 12 years of age.

About the Event Series

This event is the second of a four-part series co-hosted by Leaps.org, the Aspen Institute Science & Society Program, and the Sabin–Aspen Vaccine Science & Policy Group, with generous support from the Gordon and Betty Moore Foundation and the Howard Hughes Medical Institute.

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Kira Peikoff
Kira Peikoff is a journalist whose work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and son.