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Two COVID-19 mRNA Vaccines Are Gamechangers

COVID-19 vaccine
The U.S. biotechnology company Moderna announced its experimental COVID-19 vaccine has a 94.5 percent efficacy rate in its phase 3 clinical trial. STR/NurPhoto via Getty Images

A medical breakthrough that could save thousands of lives and effectively quash the deadliest pandemic in more than a century is imminent, it seems. And all it took to reach this point — besides the incalculable pain and suffering of millions of people worldwide — was the talent of a veritable army of scientists, a push in the back and some crafty maneuvering by the U.S. government, a good idea that wouldn't go away, and billions and billions and billions of dollars.

"The amount of resources that are being applied to this is just unprecedented," says Jim Richardson, the senior scientific liaison at U.S. Pharmacopeia, a 200-year-old scientific nonprofit that establishes federally enforced quality standards for, among other products, vaccines. "Billions of dollars have never been, in such a short time, applied to a problem of this magnitude, even with H1N1 and other things that have happened over the years. This has really spurred a lot of a variety of different platforms that people have been working on for a long time."

Dozens of companies, using several different scientific methods, have been gobbling up those government dollars (and quite a bit of private capital, too) in order to create a vaccine to stop the coronavirus that's behind the pandemic. It's obviously important work: The virus that causes COVID-19 has infected (as of this publishing) more than 56 million people in the world and killed more than 1.3 million. It's responsible for more than 250,000 deaths in the U.S. alone.

Two of the companies, in particular, that are trying to create a COVID-19 vaccine have stood out from the competition by employing a bold, still unproven process.

This time, it just might work.

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Fast-tracking a Vaccine

Before the coronavirus that causes COVID-19 reared its spiky head early in 2020, creating vaccines was a painstaking, yearslong process. The mumps vaccine was rolled out in 1967 in what is considered the fastest implementation in history. It took four years.

The vaccine for this coronavirus (officially, the severe acute respiratory syndrome coronavirus 2, or SARS-CoV-2) is on a much, much faster track, for a few reasons.

One, scientists have seen a virus like this one before: The SARS outbreak in 2003 infected more than 8,000 people worldwide and killed nearly 800. This SARS-CoV-2 virus, it turns out, is 80 percent identical in genetic material to the one in 2003. All researchers needed this time was to see how this virus was different from the last one. The Chinese scientists who discovered the SARS-2 virus in January mapped its genomes almost immediately and provided everyone a text file of its complete set of DNA.

Two, the pair of companies leading the race for a vaccine — Moderna, which is in partnership with the National Institutes of Health, and Pfizer, which is working with a German firm, BioNtech — finally seem to have perfected a once-dismissed idea for a vaccine to attack the virus. The new method of making a vaccine (more on that below) is simply much quicker than the old one.

And three ... well, those billions and billions of dollars certainly lit a fire.

COVID-19 vaccine
A volunteer in Hollywood, Florida, receives a COVID-19 vaccine during the phase 3 vaccine clinical trials.
CHANDAN KHANNA/AFP via Getty Images

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The New Vaccine and the mRNA Way

To understand these new vaccines, you have to understand the old ones. Traditional vaccines typically use a weakened (or attenuated) form of the offending virus to nudge along a person's natural ability to combat sickness. The "dead" virus is injected into the body, the immune system kicks into high gear to fight it, and when the real virus attacks, in best-case scenarios, our bodies are ready for it.

Moderna and Pfizer are using something different, something called synthetic messenger ribonucleic acid — mRNA — instead of a virus to do the same thing: push our bodies into producing antibodies to attack and neutralize the spiky coronavirus before it hooks onto healthy cells and gets us sick.

Brilliant? Sure. But potentially, it's way more than that. It's game-changing. Lifesaving.

You've probably heard of DNA, that double-helix molecule found in every cell that contains your unique genetic code. But mRNA? As its name flat-out states, it's a kind of messenger. From Moderna's site:

mRNA is a single-stranded molecule that carries genetic code from DNA in a cell's nucleus to ribosomes, the cell's protein-making machinery.

"If DNA is the big instruction manual for the cell," Paula Cannon, an associate professor of microbiology at the University of Southern California's Keck School of Medicine, told NBC News, "then messenger RNA is like when you photocopy just one page that you need and take that into your workshop."

COVID-19 vaccine
Both Pfizer and Moderna's vaccines work with mRNA technology, which is different from traditional vaccines. This chart from Vanderbilt University compares the two.
Vanderbilt University/CC BY-SA

This is how an mRNA vaccine works:

  1. Scientists target the "spikes" on the coronavirus — they're actually proteins — that enable it to latch onto healthy cells. (By the way, it's called a coronavirus because these spiky protrusions look like coronas ... something that suggests a halo, or crown. And COVID-19, also by the way, is shorthand for coronavirus disease 2019.)
  2. The synthetic mRNA in the new vaccines carries the code for this spiky protein. It's introduced into a healthy body, where it takes this message and joins up with the protein-making ribosomes in cells to manufacture the spiky proteins. That prompts our bodies to produce antibodies to kill these strange proteins, especially when they come attached to a real, invading coronavirus.
  3. Without their spikes, the coronavirus can't live and reproduce. End of story.

The advantages of the mRNA method are many. On the business end, it's cheaper to produce a bunch of mRNA strands than it is to grow a bunch of viruses, kill them off and build a vaccine around them. Without all those labor-intensive and time-eating steps, it's faster, too. On the health side, mRNA is probably less dangerous than infecting people with a weakened or dead virus. And, best of all, according to the latest data, it may be more effective.

The disadvantages ... well, there are some. The biggest: It's never been done before. mRNA technology, though it's been around for at least a couple of decades, has never been used in a vaccine. It's got a lot of proving to do.

COVID-19 vaccine
mRNA is one type of RNA found in the cell. It's made in the nucleus and then exported to the cytoplasm where the translation machinery binds to these mRNA molecules and reads the code on the mRNA to make a specific protein.
National Human Genome Research Institute

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What Lies Ahead

Late-stage testing on Moderna's and Pfizer's work, as of mid-November 2020, has been exceedingly promising. Both the Pfizer and Moderna mRNA vaccines have proven better than 90 percent effective. Moderna, which enrolled 30,000 adult U.S. participants, reported that just five of the 95 total COVID-19 cases occurred among the vaccinated — the other 90 infections were from the placebo group. That equates to a 94.5 percent efficacy rate. None of the infected patients who received the vaccine developed severe COVID-19. Pfizer saw similar results in its phase 3 trial.

In the trials the vaccines also seemed to do more than simply ward off COVID-19. They have shown that they may reduce the rate of infection, too, keeping those with the virus from spewing it to others around them.

Both companies are expected to apply for something called an Emergency Use Authorization from the U.S. Food and Drug Administration. If granted, they'll ramp up production on the vaccines. Millions of doses might be available by the end of 2020 and, if everything goes right, several billion could be ready by the first half of 2021.

Hurdles remain. Manufacturing must increase at levels never before attempted. (Most vaccine candidates now in late-stage trials take two doses to be effective.) Shipping and storing these mRNA vaccines must be ironed out. The Pfizer mRNA vaccine requires it be stored at -94 degrees Fahrenheit (-34 degrees Celsius), and it degrades after about five days at temperatures of just above freezing. Moderna's however, supposedly can be stored at 36 to 46 degrees Fahrenheit (2 to 8 degrees Celsius) for up to 30 days, and remain stable at -4 degrees Fahrenheit (-20 degrees Celsius) for up to six months. Determining who's first in line — what countries, which people — is, in many places, still to be determined.

In the meantime, other companies are deep in research and development using mRNA and more traditional methods to bring vaccines to market. Some 54 vaccines are in clinical trials in humans, according to The New York Times, and at least 87 are in preclinical trials in animals.

"The mRNA methods, now that we have the efficacy numbers, are now in the lead," Richardson says. "But there are many different candidates. There will likely be multiple vaccines that are licensed and available to the public. Who knows what the landscape will be in a year? We may have five or six or more to choose from, just like flu vaccines. And because you need so much, you need multiple manufacturers."

The pace has been breathtaking. Faced with one of the deadliest outbreaks of disease in many lifetimes, the government and private sector have joined forces to come up with a possible answer in record time. And what we've learned may help us handle the next virus that comes along.

"The speed, the number of vaccine development corollary effects — bioprocessing, knowing how to scale up, the coordination with the regulatory bodies like FDA and other organizations across the world — I think those will pay benefits for years to come," Richardson says.

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