Santa Cruz Sentinel

Years of groundwork laid for speedy vaccines

- By Lauran Neergaard

How could scientists race out COVID-19 vaccines so fast without cutting corners? A head start helped — over a decade of behindthe- scenes research that had new vaccine technology poised for a challenge just as the coronaviru­s erupted.

“The speed is a reflection of years of work that went before,” Dr. Anthony Fauci, the top U.S. infectious disease expert, told The Associated Press. “That’s what the public has to understand.”

Creating vaccines and having results from rigorous studies less than a year after the world discovered a never-before-seen disease is incredible, cutting years off normal developmen­t. But the two U.S. frontrunne­rs are made in a way that promises speedier developmen­t may become the norm — especially if they prove to work long-term as well as early testing suggests.

“Abject giddiness,” is how Dr. C. Buddy Creech, a Vanderbilt University vaccine expert, described scientists’ reactions when separate studies showed the two candidates were about 95% effective.

“I think we enter into a golden age of vaccinolog­y by having these types of new technologi­es,” Creech said at a briefing of the Infectious Diseases Society of America.

Both shots — one made by Pfizer and BioNTech, the other by Moderna and the National Institutes of Health — are so-called messenger RNA, or mRNA, vaccines, a brand-new technology. U. S. regulators are set to decide this month whether to allow emergency use, paving the way for rationed shots that will start with health workers and

nursing home residents.

Billions in company and government funding certainly sped up vaccine developmen­t — and the unfortunat­ely huge number of infections meant scientists didn’t have to wait long to learn the shots appeared to be working.

But long before COVID-19 was on the radar, the groundwork was laid in large part by two different streams of research, one at the NIH and the other at the University of Pennsylvan­ia — and because scientists had learned a bit about other coronaviru­ses from prior SARS and MERS outbreaks.

“W hen the pandemic started, we were on a strong footing both in terms of the science” and experience handling mRNA, said Dr. Tal Zaks, chief medical officer of Massachuse­tts-based Moderna.

Traditiona­lly, making vaccines required growing viruses or pieces of viruses — often in giant vats of cells or, like most flu shots, in chicken eggs — and then purifying them before next steps in brewing shots.

The mRNA approach is radically different. It starts with a snippet of genetic code that carries instructio­ns for making proteins. Pick the right virus protein to target, and the body turns into a mini vaccine factory.

“Instead of growing up a virus in a 50,000-liter drum and inactivati­ng it, we could deliver RNA and our bodies make the protein, which starts the immune response,” said Penn’s Dr. Drew Weissman.

Fifteen years ago, Weissman’s lab was trying to harness mRNA to make a variety of drugs and vaccines. But researcher­s found simply injecting the genetic code into animals caused harmful inflammati­on.

Weissman and a Penn colleague now at BioNTech, Katalin Kariko, figured out a tiny modificati­on to a building block of lab-grown RNA that let it slip undetected past inflammati­on-triggering sentinels.

“They could essentiall­y make a stealth RNA,” said Pfizer chief scientific officer Dr. Philip Dormitzer.

Other researcher­s added a fat coating, called lipid nanopartic­les, that helped stealth RNA easily get inside cells and start production of the target protein.

Meanwhile at the NIH, Dr. Barney Graham’s team figured out the right target — how to use the aptly named “spike” protein that coats the coronaviru­s to properly prime the immune system.

The right design is critical. It turns out the surface proteins that let a variety of viruses latch onto human cells are shape- shifters — rearrangin­g their form before and after they’ve fused into place. Brew a vaccine using the wrong shape and it won’t block infection.

“You could put the same molecule in one way and the same molecule in another way and get an entirely different response,” Fauci explained.

 ?? TAIMY ALVAREZ — THE ASSOCIATED PRESS ?? Blood samples from volunteers participat­ing in the Moderna COVID-19 vaccine third phase clinical trail wait to be processed in a lab at the University of Miami Miller School of Medicine.
TAIMY ALVAREZ — THE ASSOCIATED PRESS Blood samples from volunteers participat­ing in the Moderna COVID-19 vaccine third phase clinical trail wait to be processed in a lab at the University of Miami Miller School of Medicine.

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