COVID-19 vaccines are safe and effective, mRNA-based vaccines like Moderna and Pfizer didn’t come out of nowhere but were developed over years through taxpayer-funded research, and today’s undergraduates may be the ones to develop solutions for tomorrow’s variants.
CU Boulder Nobel laureate and Distinguished Professor Tom Cech (aka Dr. RNA) made these and other points during a lecture titled “The Magic of RNA: From CRISPR to Coronavirus Vaccines" via Zoom last week. Sponsored by the CU Boulder Retired Faculty Association, the presentation was viewed by more than 1,300 attendees.
“CRISPR genome editing and messenger RNA vaccines are two of the most spectacular scientific achievements since putting a man on the moon,” said Cech, who was awarded the Nobel Prize in 1989 for his research on the catalytic properties of RNA (ribonucleic acid). Key to making both technologies work, RNA also happens to be Cech’s “favorite molecule.”
After providing a glimpse of the sweeping potential of the gene-editing tool CRISPR - from preventing devastating genetic diseases to expediting scientific discovery - Cech turned to the science behind the new vaccines. Questions poured in, including one about whether an mRNA (messenger RNA) vaccine can alter a person’s DNA.
“It is not even a possibility,” he said. “With the RNA vaccines, there is no DNA being introduced.”
Cech explained how mRNA vaccines like those made by Moderna and Pfizer-BioNTech differ from other vaccines. While the Johnson & Johnson vaccine, for instance, delivers a very weakened form of the coronavirus itself, mRNA vaccines “short-circuit this pathway,” simply presenting the mRNA -- or instructions to make the spike protein, and skipping DNA all together. Our immune cells can ‘see’ and fight off coronavirus infection. But the vaccines themselves are not infectious.
“I am so excited that the first vaccines to be approved were the messenger RNA vaccines,” he said.
When the human body detects COVID-19’s spike protein, it activates B cells (bone marrow cells) to make antibodies that bind with the spike protein and prevent it from entering human cells, Cech said. The mRNA vaccines also trigger the body’s T cells (thymus cells), which attack and kill infected cells.
“Vaccines are generally the safest of all approved drugs you’ve heard of,” Cech said, adding that all the rigorous testing and safety measures are necessary due to the huge number of otherwise healthy people who will get the jab. “They have to be tested thoroughly before being FDA approved. They continue to be monitored for many years after they are marketed.”
Cech encouraged young adults to get vaccinated, even though they are least likely to suffer severe outcomes from coronavirus. That’s because COVID-19 vaccines can give 10 times more protection from future infection than the antibodies gained from a mild case.
Another advantage to mRNA vaccines: They are easy to adapt in the face of new variants, he said.
“Any undergrad in my lab, if given the sequence of the new variant, could design a vaccine against it in a week,” he said.
In the future, mRNA could be a bellwether for a whole new type of vaccine.
“I think this is really revolutionary,” he said. “Eventually, we may see a much better flu vaccine… maybe even a cancer vaccine of some sort might come out of this. It’s too early to declare victory. We need more students and research fellows working on RNA before we can really explore all the myriad of possibilities that are really opened up to us.”
A sped-up vaccine timeline
Cech expressed his amazement that scientists and researchers were able to get COVID-19 vaccines approved and in people’s arms within one year - a process that can take up to eight years. No mRNA vaccine had yet been approved, which makes this medical success that much more notable, he said.
“What are the chances the first one would be successful?” he said, noting that it’s like stepping up to the plate and hitting a home run when the first ball is pitched. “There has to be some luck involved.”
Cech touted the importance of taxpayer dollars, which funded the fundamental research into how RNA works, independent of any actual applications or a global pandemic. The fact that the groundwork was there made it possible to create a vaccine quickly (with, perhaps, a little luck, too).
Cech gave a nod to a couple CU Boulder colleagues, whose research was also instrumental to paving the way for today’s COVID vaccines.
Marv Caruthers, distinguished biochemistry professor, invented the chemical synthesis of small DNA fragments called oligonucleotides that are essential for sequencing the code of the coronavirus spike protein; and biochemist and Professor Emeritus Olke Uhlenbeck developed in vitro transcription into a robust technology that makes the mRNA vaccines possible.
While the rapid pace of vaccine development and rollout has been extraordinary, it has also been flawed, Cech said.
“mRNA vaccines are a new modality, so manufacturing and supplying them was more challenging than with a traditional vaccine,” he said, noting that the cold storage requirements also pose some distribution hurdles.
The other fundamental question on everyone’s minds is: How long will the mRNA vaccines last and how effective are they against mutations? Only research will tell, and Cech believes these are questions that undergraduates in his lab might just be able to answer.