In February, scientists from the University of Pittsburgh began searching their library of human antibodies for those that could tame the novel COVID-19 virus. With about 1 trillion antibodies to sort, it was like looking for a needle in a haystack.
They found one in less than a week using techniques that did not require waiting for samples from infected patients who had survived the disease. This is the traditional route to effective antibody treatments.
In doing so, they added another chapter to the scientific advances demonstrated during the race against the coronavirus, which has resulted in the development of several promising vaccines in record time and armed science with effective weapons against future viral threats.
On the hunt
Pitt scientists confronted COVID-19 with the benefits of having a powerful tool to quickly find antibodies with specific characteristics and a large, diverse collection of antibodies that can be screened.
With the help of the “phage display”, they were able to study the interaction of proteins on a large scale. Billions of proteins such as B. Antibodies, could be scanned in a week or less to identify those that meet certain specifications – in this case, COVID-19 neutralization. The technology won a Nobel Prize in 2018 for George Smith, a scientist from the University of Missouri, and Sir Gregory Winter of the University of Cambridge.
The size and variety of antibody libraries that researchers have available to browse are critical to quickly finding candidates with traits that offer them the best chance of preventing and treating certain viruses.
In the past few years, researchers at Pitt’s School of Medicine had built one of the world’s largest libraries of antibodies: 10 separate libraries in which more than a trillion antibodies – all human cells – are kept locked up in a freezer.
With such a large collection of antibodies, the challenge is to find a way to efficiently weed out those that do not fit the profile that scientists are looking for and identify those who do. “It’s an art,” said John Mellors, director of the infectious disease division at Pitt’s School of Medicine. “It’s like looking for gold. But it’s like searching the entire Colorado River for gold. “
A team of scientists led by Dimiter Dimitrov has found a way. For starters, they had a good idea of what to look out for in January when Chinese scientists sequenced SARS-CoV-2, the coronavirus behind the COVID-19 pandemic.
More than a decade earlier, Dr. Dimitrov’s team is studying a similar coronavirus, SARS-CoV, that caused a small international outbreak in 2003. They learned how its spike protein enables the virus to enter human cells and that part of it can be used to identify antibodies that will help fight the disease. This tiny piece of the puzzle became their guide as they searched for one that could be used against COVID-19.
“If the [COVID-19] Sequence became available, we immediately did that little part. We had the bait. “said Dr. Dimitrov, director of the Center for Antibody Therapeutics at the University of Pittsburgh.
Most of the antibodies in Pitt’s huge collection did not respond to the bait, suggesting they might prevent the virus from attaching to and invading cells, which is key to neutralization. But some made promises. The researchers analyzed top candidates and identified the strongest of the batch they named ab1.
It only took them six days to discover it.
In the months that followed, they tested it on hamsters, normal mice, and mice genetically engineered to attack cells using the COVID-19 entry point. The tests showed that ab1 was effective in preventing COVID and treating infected animals to aid their recovery.
Clinical trials testing ab1 in humans are expected to begin early next year.
Science marches on
In the race against COVID-19, several antibody treatments have emerged recently, including promising monoclonal antibodies. Monoclonal antibodies, as identified by Pitt scientists, are laboratory-made proteins designed to ward off certain viruses or other harmful invaders.
In November, the U.S. Food and Drug Administration approved the emergency use of two monoclonal antibody therapies in COVID patients. Bamlanivimab and a cocktail of the monoclonal antibodies casirivimab and imdevimab have been approved for use in patients with mild to moderate cases of the virus. Clinical studies suggested they can prevent infected patients from developing severe cases of the virus that lead to hospitalization.
Monoclonal antibody therapies are generally more expensive and difficult to perform than traditional treatments that use antibodies from surviving COVID patients whose bodies they made after infection. However, monoclonal antibodies have several advantages, including speeding up the response to a new virus. Rather than waiting for samples from people infected with a virus, once the genetic sequence of the virus is known, researchers can make monoclonal antibodies in the laboratory and speed up treatment development.
As important as this development is, the most famous scientific achievement of this pandemic year is the amazingly rapid development of promising vaccines that could prevent people from becoming infected with COVID-19 as a whole.
Antiviral vaccines typically take years, if not decades, to reach patients. So far, the mumps vaccine has been the quickest route from the laboratory to approved clinical use, and it took four years. However, a COVID-19 vaccine developed by Pfizer and German drug maker BioNTech was already approved for use in the UK in an emergency after the company reported clinical studies indicated that it was, on average, 95 percent effective against infections. Another company, Moderna, reported similar results for its COVID vaccine.
Both are awaiting FDA approval for use in the United States. Both drug makers said they could start vaccinating patients by the end of the year. Both vaccines use a synthetic form of the coronavirus genetic material, mRNA, to program a person’s cells to fight off the virus, a technology that has never been approved for such use.
Questions remain as to how long the vaccines will protect patients from the virus. However, the new vaccine platforms, antibody therapies, and remarkably efficient methods of discovering them show how scientific advances in the teeth of the COVID-19 pandemic have sharpened the ability of medicine to respond more quickly to dangerous pathogens now and in the future.
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