The spread of the virus and the public’s attention to science helped to shorten the timeline
Cuts in time spent waiting on experimental results and public interest in science accelerated COVID-19 vaccine development.
Six months after the first COVID-19 shots started going into arms in the United States, the pace of vaccination has slowed. That’s prompted White House officials to scale back their goal of getting at least one dose to 70 percent of all U.S. adults by July 4; they’re now aiming for 70 percent of those 27 and older.
Even so, more than 1 in 5 Americans say they won’t get vaccinated, according to a recent poll by the American Psychiatric Association. Among the reasons that often pop up are worries that the vaccines were developed too fast: Normally, drug research takes years or even decades from idea to reality. The first vaccines to combat COVID-19 were developed, tested and given emergency use authorization in 11 months.
Driven by a global urgency and underpinned by decades of prior work on vaccine technology, vaccine developers found a way to chop not just days or months, but years off the timeline (SN: 2/21/20). What was jettisoned was not the science, or the safety tests, but rather the wait time baked into the development process — waiting for results and waiting for regulatory approvals.
By comparing the new vaccines with earlier drugs that have used the same tech under more traditional research timelines, it is possible to calculate approximately how much time got chopped off the development process once shots were ready to go into arms: roughly four years. Here’s how.
Unlocking the coronavirus’ secrets
To back up a bit first, designing the vaccines began far earlier than the jabs-in-arms stage. It began with deciphering the exact genetic makeup of SARS-CoV-2, the virus that causes COVID-19 (SN: 12/11/20). By early January 2020, that genetic blueprint was in hand and the first vaccines to test were ready just a few weeks later.
illustration of a spike protein on the surface of a virus
For some perspective, researchers first deciphered, or sequenced, the entire human genome over a span of almost 13 years, starting in 1990 and wrapping up in 2003. Because of advances in computers, the same task now can take only hours.
Most crucially, researchers now had the genetic instructions for making the spike proteins that the virus uses to break into cells — a key ingredient for making the vaccines. Jutting out from the virus’ surface, these spike proteins make an easy target for the immune system to recognize. Researchers knew to zero in on those proteins thanks to decades of work studying coronaviruses, including two that have caused other outbreaks of human diseases — SARS and MERS. That work also identified the best form of the protein to use: a stable form just before the virus fuses with a cell it’s about to infect.
Finding a delivery system
Those instructions could then be fed directly into pre-made delivery vehicles that carry the genetic code to cells to induce an immune response. Scientists had already built these rapid, genetically based templates largely because of the ongoing battle against HIV, says Tom Denny, Chief Operating Officer of the Duke Human Vaccine Institute in Durham, N.C.
“In the last 10 to 15 years, there’ve been major teams around the world … trying to understand what needed to occur to make a protective HIV vaccine,” Denny says. Those efforts have “helped us in our battle with this current pandemic.”
These vehicles are like the Potato Head toys of the vaccine development world: Instead of swapping in different facial features, information specific to each virus gets plugged in.
Denny calls it “plug-and-play” vaccine manufacturing. Decades of trying to attack HIV has created a library of safe weapons to use quickly against any new would-be viral marauders. “We got lucky,” Denny says, that the developed platforms have worked so well for this new deadly virus.
One of the templates directly carries a nonfunctional, partial strand of viral mRNA to cells in the body, delivering instructions for those cells to create copies of the protein that the immune system recognizes as foreign. That’s what’s used in the Pfizer-BioNTech and Moderna shots.
The mRNA for the coronavirus’ spike proteins gets packaged inside tiny bubbles of fat called lipid nanoparticles. These tiny fat bubbles have been around for decades and safely used for dozens of other drugs, some approved, others still in the pipeline. So all that needed to be changed to target SARS-CoV-2 were the directions nestled inside.
The contents of the fat bubbles are known as their “payload,” says Vicki Stronge. She’s the director of product management at Precision NanoSystems in Vancouver, which manufactures equipment and compounds for the development of lipid nanoparticles. She explains why those fat bubbles are so crucial: If the mRNA is injected alone outside a bubble, it breaks down quickly, degrading into harmless biological raw bits and pieces that get recycled by our bodies.
Benefiting from past research
Two key therapies — one still in the works and one approved — paved the way for COVID-19 vaccine developers to hit the ground running with RNA-based templates.
One therapy, made by Germany-based CureVac, is the first vaccine to reach human trials that was developed using mRNA to fight an infectious disease. It targets the rabies virus and was injected into human volunteers starting in 2013. Decades earlier, in 1971, researchers developed the first syringefuls that they thought were safe for humans, which they initially tested by injecting themselves. The first version of the mRNA-based rabies vaccine prompted only a weak immune system response but did show that the technology was safe. A newer version of this rabies vaccine is starting to show promising results in clinical trials. (CureVac is also developing an mRNA COVID-19 vaccine, although early results have been disappointing.)