As the two Covid-19 vaccines start to arrive in communities across the country, they’re accompanied by questions about how they work and how they were created so quickly.

Two researchers in the Wallace H. Coulter Department of Biomedical Engineering work with the components that make up the vaccine and say they’re safe and effective.

 

1. Both the Moderna and Pfizer-BioNTech vaccines are made with mRNA. What is an mRNA vaccine?

These vaccines are made of two primary ingredients: a piece of mRNA and a lipid nanoparticle, which is made from different fats.

The mRNA is essentially a set of instructions — the “m” stands for “messenger.” In this case, the instructions tell our own cells how to make a piece of protein from the SARS-CoV-2 virus called the spike protein.

“If you ever see pictures of the coronavirus, this protein is the big spike that is sticking out of the virus particle,” said Philip Santangelo, professor in the Coulter Department.

First, the mRNA has to enter your cells, which is where the lipid nanoparticle, or LNP, comes in: It’s like an envelope that delivers the instructions. The LNP is a combination of four different fats to create a shell around the mRNA that allows it to penetrate into our cells.

“If you just inject mRNA on its own, your body does not like that, and the mRNA will not enter your cells,” said James Dahlman, assistant professor in the Department. “You can imagine the lipid nanoparticle as a Trojan horse for the mRNA: The mRNA has to enter a cell to work as a drug, but it cannot enter the cell on its own. So, you put the mRNA inside the LNP, which can enter the cell, and as a result the mRNA enters the cell.”

Once the mRNA is inside, the cells start to produce the spike protein. Your body recognizes an invader and starts to mount an immune response.

 

2. Can I get Covid-19 from the vaccine?

No. The Covid-19 vaccines contain no virus.

“The mRNA is only making the spike protein. It’s not the whole virus; it’s only a part of it,” Santangelo said. “You can’t get the virus from the mRNA vaccine.”

 

3. What about the bad reactions some people have experienced?

Santangelo said some people have had reactions at the injection site, but that’s common with many vaccines and, while annoying, it usually means the vaccine is doing exactly what it’s intended to do: prompting your body to react.

“The needle and the lipids do cause a little inflammation,” he said. “That’s what tells the immune system, ‘Hey, we need to send some cells to the muscle to pick up that spike protein,’ and then initiate the immunological responses. Then, when your body sees that protein [again] if you’re exposed to Covid-19, your body will respond rapidly and help clear the infection.”

 

4. Are any human cells used to create the vaccines?

No. The two parts of the vaccine are made in labs using readily available, purified ingredients —and no human or animal tissue, Santangelo said.

The mRNA particles are just like the RNA made in our bodies, he said, but they are assembled chemically in a lab using natural proteins.

Dahlman said the four parts of the lipid nanoparticle are either naturally occurring — like cholesterol — or designed by scientists in the lab.

 

5. How were the vaccines developed so quickly?

Two reasons, according to Dahlman and Santangelo.

First: The pharmaceutical companies had a head start.

“Both companies had lipid formulations they knew would be useful for delivering mRNA via an intramuscular injection,” Santangelo said. At that point, they just needed to know what kind of mRNA to use.

“One of the reasons why this platform is so exciting is that it is somewhat plug-and-play,” he said. “As soon as they had information about the sequence for that spike protein, the companies were easily able to put that into their pipelines and generate an mRNA for that spike. Then all they had to do was make that mRNA and combine it with the same lipids that they had been using before.”

The government and the pharmaceutical industry also had been planning for some kind of pandemic to happen eventually — most likely a flu — and conducting research on mRNA vaccines, Dahlman said.

“Did we know it was going to be Covid-19? No, we didn’t. But scientists had an idea that something could come along,” he said. “There’s been a lot of research ahead of time to study whether mRNA-based vaccines would work against emerging diseases.”

The second reason the vaccine came together quickly was a result of the design of the clinical trials, according to Dahlman. The companies designed the phase 2 and phase 3 trials at the same time as the initial trials were underway. That’s usually a prohibitively expensive proposition.

“In this case, there was a global emergency, so companies and governments took on the financial risk to design the phase 2 and phase 3 clinical trials earlier,” Dahlman said. “It was worth the risk to have the vaccine move along more quickly, given the dire human and economic consequences of this pandemic.”

 

6. How do we know the vaccines are safe?

Dahlman and Santangelo pointed to the tens of thousands of people involved in those clinical trials.

“Just because the clinical trials were run more quickly than normal does not mean the data are unreliable,” Dahlman said. “The data have been peer-reviewed. The data are clear: The vaccine is safe.”

He and Santangelo also pointed to the short amount of time the vaccine’s components remain in the human body.

“mRNA does not last forever,” Santangelo said. “The mRNA may express for a few days, and it will degrade through normal processes inherent to every cell in your body. The lipids also are metabolized through normal metabolization pathways.”

He added: “We want the vaccine to go in, to express the viral protein — the spike protein — you want your body to react to that, you want your immune system to mobilize in response to that spike being there. But we don’t want the vaccine there forever. You’re relying on your immune system to do the heavy lifting; the vaccine just gets things started.”

 

7. Why do we get two doses of the vaccine instead of one?

Santangelo said it’s not uncommon for vaccines to require multiple doses. Think of the booster shots kids receive for some vaccines.

In the case of the Covid-19 vaccine, he said: “The data suggests that after one shot, there is an immune response, but it’s not as strong as they would like, and that’s why they give you the second one. The second one is a booster. And what you see in the data is your antibody responses increase significantly.”

 

8. Why do the vaccines have to be stored at such cold temperatures?

The Pfizer-BioNTech vaccine has to be stored at -70 degrees Celsius. Moderna’s is frozen at -25 degrees Celsius. That’s all about preserving the stability and effectiveness of the vaccine, Santangelo said, and the difference is attributable to the different kinds of lipids the two companies used around the mRNA.

It may not be ideal, but Santangelo said the requirements keep the vaccine from degrading in any way.

“They had to move so fast creating the vaccines, so they went with what they knew would work,” he said.

 

9. How long will protection last from the vaccine?

We don’t have as much information about the durability of protection as we would like, Santangelo said. He pointed to data that shows persistence of antibodies for at least three to six months after the second dose.

Even with that question still unanswered, he said getting the vaccine will benefit everyone.

“It’s going to help protect you from the virus,” he said. “Even if you get Covid — not from the vaccine, but post-vaccination — you’re not going to get as sick if you have the vaccine than if you didn’t have the vaccine. If the vaccine keeps us out of the hospital, if it keeps us from getting very, very sick, that is a very good thing.”