I wanted to understand how these new mRNA vaccines work and get answers to some of the questions I had, so I pulled in an expert: John D. Lueck, PhD.
Lueck is an Assistant Professor at the University of Rochester Medical Center where he runs a lab specializing in biophysics and gene therapy. He works with RNA and hopes his discovery based research will result in therapies for people with cystic fibrosis and myotonic dystrophy. He’s quick to point out that he’s not an immunologist and that the immune system is a magical wonderland that is super complicated. That said, he was happy to answer my questions and give me an overview of how mRNA vaccines work. “I’ve never been more confident in a vaccine to be honest with you,” Lueck said.
Thank you Katalin Karikó and Drew Weissman
mRNA technology wasn’t invented yesterday or a year ago or even a decade ago. It has been around for a while.
Katalin Karikó and Drew Weissman made the COVID-19 mRNA vaccine a reality by figuring out a way to modify mRNA so that it can accomplish its goal of delivering important info to the cells. This part gets very science-y, but my understanding is that if you want mRNA to deliver material to a cell, it’s not great if it gets blasted to bits before it gets a chance to ring the doorbell. These two brainy scientists engineered a way to shield mRNA from immune system attack by swapping out one molecule with another that looks the same, but doesn’t invoke the wrath of the immune system.
There was very little fanfare when Weissman and Karikó published their paper in 2005. At least one person was paying attention, though, Derrick Rossi. Wait a minute, is that the same Derrick Rossi that co-founded Moderna in 2010, the makers of one of the two big mRNA vaccines for COVID-19? Why, yes it is. Derrick Rossi says Karikó and Weissman deserve the Nobel Prize in chemistry.
This is not our first rodeo (with a coronavirus)
Operation Warp Speed is a program that was created by the U.S. Government to develop, manufacture and distribute COVID-19 vaccines. When I hear the words “Operation Warp Speed” I also hear Scotty yelling, “I’m giving her all she’s got, Captain!” while the Starship Enterprise tilts, sparks fly out of the console and at least one nameless crew member falls to the ground.
People are rightfully wondering if the vaccine process was rushed. Vaccines normally take more than one year to get to market. More like 10-15 years. However, it’s also true that coronavirus vaccines were already in the works when COVID-19 showed up. After SARS in 2002 and MERS in 2012, scientists were on it, because they guessed another coronavirus would appear soon. They paid special attention to the coronavirus spike protein and they were able to apply lessons learned from the original SARS to Sars-CoV-2 (a.k.a. COVID-19).
So yes, from the appearance of the first cases of COVID-19 to now is less than a year, which feels like a very short turnaround for a lifesaving vaccine, but there was lot of science happening beforehand. “It seems super fast and not thought through, but that’s not the case, it’s just that science is so vast and efficient and awesome now, that all these things that took so long before, they’re not roadblocks anymore,” Lueck says.
Tell me more about COVID-19
Lueck describes the Covid-19 virus as a kind of like a Koosh ball. A Koosh ball covered in proteins. Its spikes bond to the outside of the cell, then it releases virus RNA into the cells and then the virus uses the cell’s own machinery to start replicating (jerk!). “The virus gets into your cells, it replicates, it bursts those cells, then goes on to the next cells. It’s a path of destruction. Your cells are being infected, ruptured, infected, ruptured,” Lueck says, adding, “That is terrifying.”
How does an mRNA vaccine work?
mRNA vaccines stop spike proteins from getting inside our cells. They do this by giving the body blueprints to build a protein that is a harmless version of the virus. This harmless virus fakes out the body and triggers an immune response which manufactures the antibodies you need to fight off the real virus if you encounter it later on. “As soon as the mRNA enters the cell it starts making the spike protein immediately. While it’s making the spike protein through a process called translation, the mRNA is degrading. As the mRNA goes away, the protein levels go up and then you arrive at a critical amount that will induce immune response,” Lueck says. “It’s incredible all these things that are going on. You’re basically hijacking an evolved biological system to make it work in your favor.”
He describes the mRNA vaccine as a police sketch artist who is drawing an image of the “bad guy.” The immune system takes a look at the sketch, checks out its features and says, “Gotcha, if I see anything like that I’m going to wrassle it to the ground.” Yes, John Lueck, PhD used the word “wrassle” and that made me laugh.
Now I’m going to pull in another expert, illustrator, Bryant Paul Johnson. After talking to Lueck, Johnson made this wonderful comic to explain how the mRNA vaccine works.
Are mRNA vaccines safe?
“Even in a controlled environment where I am adding mRNA to a dish of cells it is hard to get it to work,” says Lueck. “For it to be toxic, it would need to work another way really efficiently. When I found out the new COVID-19 vaccines were RNA, I was like this is way safer than attenuated virus or any other sort of vaccine.”
In short: mRNA is fragile. It is broken down by the body very quickly. It cannot make a virus.
The Phase 3 trial of the mRNA vaccines from Pfizer and Moderna included over 70,000 volunteers. Pfizer had 44,000 volunteers and Moderna had 30,000. Half of the volunteers received a placebo injection, so that means 37,000 people received the real deal. No serious safety concerns came up.
The piece of information we don’t have is what the long term-effect of the vaccine is. Usually volunteers are tracked for two years after they receive a new vaccine before that vaccine is approved. However, a quick glance at the Johns Hopkins COVID-19 map shows that we are in a serious situation where the risk of waiting a couple of years outweighs the risk of moving forward. The good news? Adverse reactions mostly show up in the first two months after vaccination and the trials have been going on longer than that (both Pfizer and Moderna started Phase 3 clinical trials in late July).
What about mutations?
COVID-19 is very good at its primary job, which is transmission. There shouldn’t be a lot of pressure on it to mutate into something more efficient. However, as we’ve seen in the UK, mutations happen. Mutations are legitimately scary, especially if they make an already infectious virus more infectious.
That said, scientists are hopeful that COVID-19 won’t mutate so much in the short term that the vaccine will stop working. If we do experience too much drift, one of the benefits of mRNA vaccine technology is that it’s easy to customize.
Will the vaccine alter my DNA?
mRNA vaccines do not affect DNA inside of the cell. “It cannot modify your genome, it can’t make virus,” Lueck says. I mentioned CRISPR to him. He explained that CRISPR is used for genetic engineering and mRNA is not like CRISPR. “CRISPR will modify your genome. That has real potential off-target effects and concerns. It’s impossible for this mRNA to modify your genome, there is no way it will do that,” Lueck says, “We’re not altering DNA here.”
Does the vaccine work?
The Pfizer vaccine and the Moderna vaccine have far exceeded everyone’s expectations. We are talking 95% efficacy for the Pfizer vaccine and over 94% efficacy for the Moderna vaccine, putting it in the same category as other gold standard vaccines (polio, yellow fever, measles). The FDA only required 50% efficacy to authorize the vaccine for emergency usage. The other good news? Subjects who got COVID-19 despite being vaccinated, didn’t get the severe kind of COVID-19 that requires hospitalization.
How long will protection from the mRNA vaccine last?
As far as I can tell, no one knows.
How does the vaccine compare to natural immunity from recovering from the virus itself?
Lueck says, “The immunity you would get after having COVID-19 is not as good as getting the vaccine. What you’re doing by giving mRNA, is that you are giving one really good target and that’s the only target for your immune system. When you have the virus itself you have many targets at lower levels and your immune system is picking on all of them, basically. The vaccine is like a beacon–it’s a strong antigen.”
Will I get COVID-19 from the vaccine?
There is 0% chance of getting COVID from the Pfizer and Moderna vaccine. However, there may be some side effects or symptoms. This is expected.
What are the side effects?
Fatigue, fever, chills, headache, soreness around the injection site. These shouldn’t last long. Expect these to occur more frequently with the second dose than the first dose. “It’s how you know your immune system is ramping up! It’s how you know it’s working,” Lueck says. However, “If you don’t get the aches and pains, this doesn’t mean the vaccine didn’t work for you. It just means that we all respond to vaccines a bit differently.”
What about those people in the UK who got an allergic reaction to the vaccine?
Experts are still working to pinpoint which ingredient in the vaccine could have caused the allergic reaction. There’s been some chatter about polyethylene glycol or PEG, but nothing definitive yet. Adverse side effects can happen with any vaccine. “The allergic reaction with PEG is synonymous with asking people if they are allergic to eggs before getting other vaccines, because other vaccines are made with egg based technology of all things. So this is nothing new, just different,” Lueck says.
If you are worried about an allergic reaction to the vaccine, please talk to your medical provider.
How about people who are immunocompromised?
Immunocompromised people were not included in the clinical trials, which is normal for vaccines. Typically this kind of testing comes after the drug has been FDA approved.
How is the vaccine given?
Both the Pfizer, Moderna vaccines are each administered in two doses. This is known as a “prime-boost” strategy. Pfizer’s two injections are given 21 days apart, Moderna’s are given 28 days apart.
As Lueck describes it, “You know when you’re pounding a nail? You first set the nail right with the first injection and you nail it in with the second one. There’s no point in getting the first injection if you don’t get the second one, efficacy goes way down. It’s so important to get the second shot.”
You need that second dose to get properly immunized.
Sign me up!
It’s going to take a while for someone like me to be able to walk into my local drugstore and get vaccinated. Maybe Spring or Summer? Getting tons of people vaccinated while also keeping them safe from contracting COVID-19 is a logistical nightmare. Adding to the complexity is the fact that the Pfizer vaccine has to be at minus-94 degrees Fahrenheit, which is colder than standard medical freezers (an ultra cold freezer can set you back $10,000). The Pfizer vaccine can survive for only about five days in the fridge after being defrosted. Each Pfizer vial contains five doses (sometimes more) and once those doses are mixed up, the solution is only good for six hours. The Moderna vaccine is more forgiving. It can be kept at -4 degrees Fahrenheit and after thawing can hang out in the fridge for a month. These “cold chain” requirements may dictate which vaccine you end up with. It sounds like you need to stick with whichever brand you start with, so if your initial shot was Moderna, your booster should also be Moderna and likewise, if your initial shot was Pfizer, your booster should be Pfizer.
I got the vaccine, now what?
I know you want to rip off that mask, frolic in a shopping mall, eat inside a restaurant and maybe like go to a rave. However, we are not there yet.
So far we don’t have proof that the vaccine suppresses transmission. If you get a vaccine, we still don’t know if you can pass the virus on. It’s also unclear if the vaccine protects against the coronavirus infection itself or just against developing symptoms once you are infected.
Also, it takes a while for the body to produce T-lymphocytes and B-lymphocytes after vaccination so you’ll still need to protect yourself while your body builds immunity. And of course we need to continue to protect others. Dr. Fauci says we need 75% to 85% of the population vaccinated to achieve herd immunity. Dr. Fauci did his part and got vaccinated on live TV.
I just ordered a couple more masks from Tom Bihn.
The future of mRNA
Right now, there are currently no licensed mRNA vaccines, but scientists have been investigating mRNA as therapies for all sorts of things. Lueck uses it in treatments for cystic fibrosis. He also mentioned that it would be a candidate for for Duchenne muscular dystrophy. The flu, Zika virus, rabies, cytomegalovirus (CMV), cancer and strokes are all possible candidates for mRNA technology. Lueck says, “I don’t think it’s going to be the answer to everything, but I think it’s going to be an answer to a lot of tough therapeutic issues that we have, for sure.”