Years of analysis laid the inspiration for quick COVID-19 recordings


How could scientists take on COVID-19 vaccines so quickly without compromising? A head start helped – over a decade of behind-the-scenes research where new vaccine technology was challenged when the coronavirus broke out.

“The speed reflects the years of work that has gone before,” said Dr. Anthony Fauci, the leading US infectious disease expert, told The Associated Press. “The public has to understand that.”

The manufacture of vaccines and the results of rigorous studies conducted less than a year after the world discovered a never-before-seen disease are incredible, and are shortening normal development by years. However, the two US front-runners are engineered so that faster development can become the norm – especially if they turn out to work long-term and early testing suggests it.

Dr. C. Buddy Creech, a vaccines expert from Vanderbilt University, described the scientists’ reactions when separate studies showed the two candidates were about 95% effective.

“I think we are entering a golden age of vaccination with these new technologies,” Creech said at a briefing for the Infectious Diseases Society of America.

Both recordings – one from Pfizer and BioNTech, the other from Moderna and the National Institutes of Health – are called messenger RNA or mRNA vaccines, a brand new technology. U.S. regulators will decide this month whether to allow the emergency and pave the way for rationed admissions starting with health workers and nursing home residents.

Billions of corporate and government funds have certainly accelerated vaccine development – and the sadly large number of infections meant scientists didn’t have to wait long to learn that the shots appeared to work.

But long before COVID-19 was on the radar, the cornerstone was in large part laid by two different research streams, one at the NIH and one at the University of Pennsylvania – and because scientists from the past had learned about other coronaviruses, SARS and MERS -Outbreaks.

“When the pandemic started, we were on solid foundations both scientifically and in terms of mRNA management,” said Dr. Tal Zaks, Chief Medical Officer of Moderna, Massachusetts.

Traditionally, making vaccines has involved growing viruses or pieces of virus – often in giant cell containers or, like most flu shots, in chicken eggs – and then cleaning them up before taking the next steps in vaccine brewing.

The mRNA approach is radically different. It starts with a snippet of genetic code that contains instructions on how to make proteins. Pick the right viral protein and the body will turn into a mini vaccine factory.

“Instead of growing a virus in a 50,000 liter drum and inactivating it, we could deliver RNA and our bodies make the protein that triggers the immune response,” said Dr. Drew Weissman from Penn.

Fifteen years ago, Weissman’s lab tried to use mRNA to make a variety of drugs and vaccines. However, researchers found that simply injecting the genetic code into animals caused harmful inflammation.

Weissman and Katalin Kariko, a colleague of Penn at BioNTech, discovered a tiny modification of a building block made of RNA grown in the laboratory, which allowed it to slide past inflammatory sentinels undetected.

“You could essentially make a stealth RNA,” said Dr. Philip Dormitzer, Pfizer’s Chief Scientific Officer.

Other researchers added a fat coating called lipid nanoparticles that helped stealth RNA get into cells easily and start producing the target protein.

Meanwhile, Dr. Barney Graham at the NIH came up with the right goal – how to use the aptly named “spike” protein that coats the coronavirus to properly activate the immune system.

The right design is crucial. It turns out that the surface proteins that allow a wide variety of viruses to attach to human cells are shape-shifters that rearrange their shape before and after they fuse. Brew a vaccine with the wrong shape and it won’t block infections.

“You could put the same molecule in one way and the same molecule in the other and get a completely different reaction,” explained Fauci.

This was a discovery in 2013 when Graham, associate director of the NIH’s Vaccine Research Center, and colleague Jason McLellan investigated a decade-old failed vaccine for RSV, a respiratory disease in children.

They looked for the right structure for an RSV protein and learned genetic enhancements that stabilized the protein in the right form for vaccine development. They applied that lesson to other viruses, including researching a vaccine against MERS, a COVID-19 cousin, though it hadn’t gotten very far at the start of the pandemic.

“That has enabled us to do this quickly,” Graham told the AP in February, before the NIH’s vaccine was first tested in humans. “Once you have this atomic-level detail, you can engineer the protein to be stable.”

In 2018, German BioNTech also worked with New York-based Pfizer to develop a more modern flu vaccine based on mRNA that would give both companies an early understanding of how to use the technology.

“That brewed everything. It was no accident, ”said Pfizers Dormitzer.

In January last year, shortly after the new coronavirus was reported in China, Ugur Sahin, CEO of BioNTech, switched gears and used the same method to make a COVID-19 vaccine.

Moderna also used mRNA to develop vaccines against other germs, including mosquito-borne Zika virus – research that has shown promise but has not moved fast since the Zika outbreak.

At the NIH, Graham woke up on Saturday January 11 to see Chinese scientists had shared the genetic map of the new coronavirus. His team had to work on the properly formed spike protein. Days later, they sent this recipe to Moderna – and the vaccination race was on.

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