Harvard Researchers Are Using a Breakthrough Tool to Find the Antibodies That Best Knock Out the Coronavirus
Lina Zeldovich has written about science, medicine and technology for Popular Science, Smithsonian, National Geographic, Scientific American, Reader’s Digest, the New York Times and other major national and international publications. A Columbia J-School alumna, she has won several awards for her stories, including the ASJA Crisis Coverage Award for Covid reporting, and has been a contributing editor at Nautilus Magazine. In 2021, Zeldovich released her first book, The Other Dark Matter, published by the University of Chicago Press, about the science and business of turning waste into wealth and health. You can find her on http://linazeldovich.com/ and @linazeldovich.
To find a cure for a deadly infectious disease in the 1995 medical thriller Outbreak, scientists extract the virus's antibodies from its original host—an African monkey.
"When a person is infected, the immune system makes antibodies kind of blindly."
The antibodies prevent the monkeys from getting sick, so doctors use these antibodies to make the therapeutic serum for humans. With SARS-CoV-2, the original hosts might be bats or pangolins, but scientists don't have access to either, so they are turning to the humans who beat the virus.
Patients who recovered from COVID-19 are valuable reservoirs of viral antibodies and may help scientists develop efficient therapeutics, says Stephen J. Elledge, professor of genetics and medicine at Harvard Medical School in Boston. Studying the structure of the antibodies floating in their blood can help understand what their immune systems did right to kill the pathogen.
When viruses invade the body, the immune system builds antibodies against them. The antibodies work like Velcro strips—they use special spots on their surface called paratopes to cling to the specific spots on the viral shell called epitopes. Once the antibodies circulating in the blood find their "match," they cling on to the virus and deactivate it.
But that process is far from simple. The epitopes and paratopes are built of various peptides that have complex shapes, are folded in specific ways, and may carry an electrical charge that repels certain molecules. Only when all of these parameters match, an antibody can get close enough to a viral particle—and shut it out.
So the immune system forges many different antibodies with varied parameters in hopes that some will work. "When a person is infected, the immune system makes antibodies kind of blindly," Elledge says. "It's doing a shotgun approach. It's not sure which ones will work, but it knows once it's made a good one that works."
Elledge and his team want to take the guessing out of the process. They are using their home-built tool VirScan to comb through the blood samples of the recovered COVID-19 patients to see what parameters the efficient antibodies should have. First developed in 2015, the VirScan has a library of epitopes found on the shells of viruses known to afflict humans, akin to a database of criminals' mug shots maintained by the police.
Originally, VirScan was meant to reveal which pathogens a person overcame throughout a lifetime, and could identify over 1,000 different strains of viruses and bacteria. When the team ran blood samples against the VirScan's library, the tool would pick out all the "usual suspects." And unlike traditional blood tests called ELISA, which can only detect one pathogen at a time, VirScan can detect all of them at once. Now, the team has updated VirScan with the SARS-CoV-2 "mug shot" and is beginning to test which antibodies from the recovered patients' blood will bind to them.
Knowing which antibodies bind best can also help fine-tune vaccines.
Obtaining blood samples was a challenge that caused some delays. "So far most of the recovered patients have been in China and those samples are hard to get," Elledge says. It also takes a person five to 10 days to develop antibodies, so the blood must be drawn at the right time during the illness. If a person is asymptomatic, it's hard to pinpoint the right moment. "We just got a couple of blood samples so we are testing now," he said. The team hopes to get some results very soon.
Elucidating the structure of efficient antibodies can help create therapeutics for COVID-19. "VirScan is a powerful technology to study antibody responses," says Harvard Medical School professor Dan Barouch, who also directs the Center for Virology and Vaccine Research. "A detailed understanding of the antibody responses to COVID-19 will help guide the design of next-generation vaccines and therapeutics."
For example, scientists can synthesize antibodies to specs and give them to patients as medicine. Once vaccines are designed, medics can use VirScan to see if those vaccinated again COVID-19 generate the necessary antibodies.
Knowing which antibodies bind best can also help fine-tune vaccines. Sometimes, viruses cause the immune system to generate antibodies that don't deactivate it. "We think the virus is trying to confuse the immune system; it is its business plan," Elledge says—so those unhelpful antibodies shouldn't be included in vaccines.
More importantly, VirScan can also tell which people have developed immunity to SARS-CoV-2 and can return to their workplaces and businesses, which is crucial to restoring the economy. Knowing one's immunity status is especially important for doctors working on the frontlines, Elledge notes. "The resistant ones can intubate the sick."
Lina Zeldovich has written about science, medicine and technology for Popular Science, Smithsonian, National Geographic, Scientific American, Reader’s Digest, the New York Times and other major national and international publications. A Columbia J-School alumna, she has won several awards for her stories, including the ASJA Crisis Coverage Award for Covid reporting, and has been a contributing editor at Nautilus Magazine. In 2021, Zeldovich released her first book, The Other Dark Matter, published by the University of Chicago Press, about the science and business of turning waste into wealth and health. You can find her on http://linazeldovich.com/ and @linazeldovich.
A startup aims to make medicines in space
Story by Big Think
On June 12, a SpaceX Falcon 9 rocket deployed 72 small satellites for customers — including the world’s first space factory.
The challenge: In 2019, pharma giant Merck revealed that an experiment on the International Space Station had shown how to make its blockbuster cancer drug Keytruda more stable. That meant it could now be administered via a shot rather than through an IV infusion.
The key to the discovery was the fact that particles behave differently when freed from the force of gravity — seeing how its drug crystalized in microgravity helped Merck figure out how to tweak its manufacturing process on Earth to produce the more stable version.
Microgravity research could potentially lead to many more discoveries like this one, or even the development of brand-new drugs, but ISS astronauts only have so much time for commercial experiments.
“There are many high-performance products that are only possible to make in zero-gravity, which is a manufacturing capability that cannot be replicated in any factory on Earth.”-- Will Bruey.
The only options for accessing microgravity (or free fall) outside of orbit, meanwhile, are parabolic airplane flights and drop towers, and those are only useful for experiments that require less than a minute in microgravity — Merck’s ISS experiment took 18 days.
The idea: In 2021, California startup Varda Space Industries announced its intention to build the world’s first space factory, to manufacture not only pharmaceuticals but other products that could benefit from being made in microgravity, such as semiconductors and fiber optic cables.
This factory would consist of a commercial satellite platform attached to two Varda-made modules. One module would contain equipment capable of autonomously manufacturing a product. The other would be a reentry capsule to bring the finished goods back to Earth.
“There are many high-performance products that are only possible to make in zero-gravity, which is a manufacturing capability that cannot be replicated in any factory on Earth,” said CEO Will Bruey, who’d previously developed and flown spacecraft for SpaceX.
“We have a team stacked with aerospace talent in the prime of their careers, focused on getting working hardware to orbit as quickly as possible,” he continued.
“[Pharmaceuticals] are the most valuable chemicals per unit mass. And they also have a large market on Earth.” -- Will Bruey, CEO of Varda Space.
What’s new? At the time, Varda said it planned to launch its first space factory in 2023, and, in what feels like a first for a space startup, it has actually hit that ambitious launch schedule.
“We have ACQUISITION OF SIGNAL,” the startup tweeted soon after the Falcon 9 launch on June 12. “The world’s first space factory’s solar panels have found the sun and it’s beginning to de-tumble.”
During the satellite’s first week in space, Varda will focus on testing its systems to make sure everything works as hoped. The second week will be dedicated to heating and cooling the old HIV-AIDS drug ritonavir repeatedly to study how its particles crystalize in microgravity.
After about a month in space, Varda will attempt to bring its first space factory back to Earth, sending it through the atmosphere at hypersonic speeds and then using a parachute system to safely land at the Department of Defense’s Utah Test and Training Range.
Looking ahead: Ultimately, Varda’s space factories could end up serving dual purposes as manufacturing facilities and hypersonic testbeds — the Air Force has already awarded the startup a contract to use its next reentry capsule to test hardware for hypersonic missiles.
But as for manufacturing other types of goods, Varda plans to stick with drugs for now.
“[Pharmaceuticals] are the most valuable chemicals per unit mass,” Bruey told CNN. “And they also have a large market on Earth.”
“You’re not going to see Varda do anything other than pharmaceuticals for the next minimum of six, seven years,” added Delian Asparouhov, Varda’s co-founder and president.
Genes that protect health with Dr. Nir Barzilai
In today’s podcast episode, I talk with Nir Barzilai, a geroscientist, which means he studies the biology of aging. Barzilai directs the Institute for Aging Research at the Albert Einstein College of Medicine.
My first question for Dr. Barzilai was: why do we age? And is there anything to be done about it? His answers were encouraging. We can’t live forever, but we have some control over the process, as he argues in his book, Age Later.
Dr. Barzilai told me that centenarians differ from the rest of us because they have unique gene mutations that help them stay healthy longer. For most of us, the words “gene mutations” spell trouble - we associate these words with cancer or neurodegenerative diseases, but apparently not all mutations are bad.
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Centenarians may have essentially won the genetic lottery, but that doesn’t mean the rest of us are predestined to have a specific lifespan and health span, or the amount of time spent living productively and enjoyably. “Aging is a mother of all diseases,” Dr. Barzilai told me. And as a disease, it can be targeted by therapeutics. Dr. Barzilai’s team is already running clinical trials on such therapeutics — and the results are promising.
More about Dr. Barzilai: He is scientific director of AFAR, American Federation for Aging Research. As part of his work, Dr. Barzilai studies families of centenarians and their genetics to learn how the rest of us can learn and benefit from their super-aging. He also organizing a clinical trial to test a specific drug that may slow aging.
Show Links
Age Later: Health Span, Life Span, and the New Science of Longevity https://www.amazon.com/Age-Later-Healthiest-Sharpest-Centenarians/dp/1250230853
American Federation for Aging Research https://www.afar.org
https://www.afar.org/nir-barzilai
https://www.einsteinmed.edu/faculty/484/nir-barzilai/
Metformin as a Tool to Target Aging
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5943638/
Benefits of Metformin in Attenuating the Hallmarks of Aging https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7347426/
The Longevity Genes Project https://www.einsteinmed.edu/centers/aging/longevity-genes-project/
Lina Zeldovich has written about science, medicine and technology for Popular Science, Smithsonian, National Geographic, Scientific American, Reader’s Digest, the New York Times and other major national and international publications. A Columbia J-School alumna, she has won several awards for her stories, including the ASJA Crisis Coverage Award for Covid reporting, and has been a contributing editor at Nautilus Magazine. In 2021, Zeldovich released her first book, The Other Dark Matter, published by the University of Chicago Press, about the science and business of turning waste into wealth and health. You can find her on http://linazeldovich.com/ and @linazeldovich.