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Pathogen Perspectives

Episode 1: mRNA Vaccines

Heather Lander  0:08  
Hey guys, this is pathogen perspectives the podcast, where we will bridge the dangerous gap between the science of infectious diseases and public misperception. So you… can keep it in perspective. I'm your host, Dr. Heather Lander.
Welcome to Episode One of pathogen perspectives. We're going to talk about messenger RNA vaccines for COVID-19. Okay, so I am so excited to finally get to talk to you guys about the COVID-19 vaccines that we have going on right now. So last week, the maternal vaccine was authorized for emergency use by the FDA. So now we have the Pfizer mRNA vaccine, and the Moderna mRNA vaccine. And this is really quite something, right? I mean, scientists have been trying to get mRNA vaccines to work for years. And it's always been a problem, because mRNA is really fragile. But these guys did it. If you follow me on Twitter, you know that I was doubtful. I thought there was no way they would get it done this fast. And I was wrong. I eat my words, they absolutely did it. They nailed it. And I have never been more thrilled to be wrong. Now, I know this is a lot to process, right. And it's still going to take time for most of us to get the vaccine. So I'd like to give you some information in this episode that will hopefully clear up any confusion or misperceptions that anybody has about mRNA vaccines, and help you feel more comfortable taking it. Because I genuinely, genuinely urge everyone to get this vaccine when it is available to you. And by the end of this episode, you will know why I feel that way. So let's get started.

[What is mRNA and how do mRNA vaccines work?]
So what is mRNA? Well, mRNA is messenger RNA. And it's the first step needed when we decode our DNA to make proteins. We use DNA to make messenger RNA and messenger RNA is used to make proteins. Using messenger RNA to make proteins is what our cells do. They are pros at it. So the idea with a messenger RNA vaccine is that we introduce messenger RNA into our cells that codes for a viral protein. Our cells will take that messenger RNA and use it to make the viral protein, that one specific viral protein. Our cells will not be able to make any other proteins for the virus than what is coded in that single messenger RNA. They will not be able to make an entire virus particle. So they are not going to cause infection with this virus, or disease caused by this virus. They simply cannot do that. For these vaccines, the messenger RNA codes for the virus spike protein, which you've probably heard of. So our cells will make copies of the virus spike protein. As copies of this virus protein accumulate in our cells, they are moved to the surface of the cell, where they are pushed through and displayed on the outside of the cell so that anybody hanging out in that area might bump into that viral protein. For example, an immune cell, maybe even an immune cell that makes antibodies. The more copies of that protein that are on the outside of our cells, the more likely that antibody generating immune cells will bump into it, and we will get more antibodies against that spike protein. And this production of antibodies is what we want. This is how our immune system prepares. So it can defend us if we're infected by the virus. As with all vaccines, this means that we are protected from COVID-19 without risking the very real dangers of infection with SARS2 and this is what we have been waiting for. Vaccines will help us end this pandemic. So this is really, really great news. And it's very exciting to see people all around the world and in the US get vaccinated.

[Can mRNA vaccines change our DNA?]
Now I know that people have concerns, and they have questions before they decide whether or not they want to get this vaccine. Let's see if I can answer some of those. One concern I've heard repeatedly and seen on Twitter and other places, is this idea that a messenger RNA vaccine can somehow change our DNA. I can tell you with absolute confidence that that cannot happen. There is no molecular mechanism by which messenger RNA can alter DNA, it is not possible. If it were possible, then the messenger RNA that's naturally in our cells would be able to change our DNA. And that does not happen. It just doesn't. The process of decoding DNA to make proteins is very strictly regulated in our cells at every point in the process. And for that reason, messenger RNA isn't allowed to hang out very long. It's, like I said, it's very fragile. And it is degraded really quickly after protein is made from it. Think of this whole process of decoding DNA into proteins, like a multi disc CD player. The CDs in this analogy, are the messenger RNA, and the player can play a CD and read the contents. But the information on the CD does not ever get integrated into the machinery of the player, nor does it affect the player. Now, if you add a foreign messenger RNA, like a virus messenger RNA to the system, it would be like putting in a new CD, the player reads it and plays it. And again, the information on the CD and the CD itself, do not affect the player. And when you're done with a CD, it's ejected. And this is how it is with messenger RNA and our DNA, the messenger RNA does its job and is degraded, it does not impact our DNA at all. It cannot.

[How do we know these mRNA vaccines are safe?]
Okay, so aside from that, how do we know that these vaccines are safe? Well, the most convincing information we have, honestly, is that the FDA has authorized emergency use of these vaccines. And while you may think that that is something that could be politically biased, or otherwise biased, the reality is that these vaccines had to pass rigorous safety standards to get this far at all. It's also important to keep in mind that as Dr. Fauci said in a press conference, safety of the vaccines is independently reviewed by something called the Data and Safety Monitoring Board. And vaccine manufacturers are not involved in that process, not at all. Now, if we just look at the data, regarding safety of these vaccines, it's excellent. We've seen nothing more than the usual expected side effects that we see with other vaccines. And those side effects include things like maybe a low fever, soreness at the injection site, maybe a little bit of just feeling crummy for a day. And that actually tells us that the immune response was triggered, the vaccine is doing its job. So those are expected side effects. And they are not concerning at all. And in fact, after the second dose, many people experience those same symptoms maybe a little bit more severe than the first time. And that's because the immune response that is triggered by the second dose is stronger than the one triggered by the first dose. And that's expected.

One really important thing to keep in mind regarding new vaccines like these is that really severe adverse events after vaccination that are truly caused by a vaccine are incredibly rare. And a vaccine trial does not have enough participants to allow us to catch one of those. So that just means that once we start vaccinating, the numbers of people vaccinated will increase from 10s of 1000s to hundreds of 1000s, to millions, and with those numbers of people vaccinated, if there are going to be any serious adverse events, we will see that. In other words, it's not until a vaccine is authorized for emergency use, or approved that we will vaccinate enough people to be able to detect an incredibly rare side effect. Importantly, the clinical trials are still collecting data on their participants. And they will continue to do so for the next two years so that we can get some long term data on protection, other side effects that might manifest later and things like that. So just because we have authorization now does not mean that we're not continuing to gather data. We are. In fact, the first waves of healthcare workers and long term care facility residents and workers are providing data for the clinical trials as well. All of this is to say that safety is being taken very seriously. These vaccines have had to pass the rigorous standards that we have for all of our vaccines.

And I know that the fact that these vaccines happened really quickly makes some people pause and think, wow, what, you know, what corners did they cut? How did they skimp to get this done so quickly? But the reality is, the science was not rushed, no corners were cut, the things that were actually expedited were administrative processes that usually take our government a very long time, because this is an emergency.

Now one last thing on safety I'd like to talk about are the cases we've heard since we started vaccinating people in the population of severe allergic reactions. So what we've seen so far are cases of allergic reactions in people with a history of severe allergic reactions. If you have a history of severe allergic reactions, talk to your doctor about the vaccine. And he or she will most likely recommend that you get the vaccine in a medical setting where they can intervene if you have a reaction to the vaccine. But so far, each of these cases resolved quickly and the person was fine. But you know, talk to your doctor and decide what's best for you.

[How do we know these mRNA vaccines are effective?]
Another question I hear a lot regarding these vaccines is how do we really know that they're effective? And the answer to that is, we have the data that tells us they're effective. And unfortunately, for many people, that means you have to take our word for it, or get comfortable with looking at the data. The good news is that the people who are deciding whether to authorize use of these vaccines are experts, they can look at the data and understand what it means and make well-informed decisions. And we just need to let them do their jobs. I can tell you that based on the data I've seen, the data presented to the FDA in the briefs for emergency use authorization, indicate that these vaccines are incredibly effective.

And that brings us to the question of well, what does effective mean? What? What does the vaccine protect us from? And for how long are we going to have that protection? So what we know for sure, is that the vaccines protect from disease. They protect someone who's vaccinated from developing COVID-19 or severe COVID-19. And this is fantastic, right? Keeping people out of hospitals and keeping people out of morgues is a win. But we also hear people asking about well, does it prevent transmission? And I want to be really clear here about what I'm talking about. So the vaccine cannot give you the virus. So you cannot transmit the vaccine. What people are asking about in this regard is if I get the vaccine, and I'm protected, but then somebody infects me with the virus, sure I won't get sick. Or maybe I get a little bit sick, but I don't get severe COVID. But can I then give my infection to somebody else? And that is something we don't have an answer for yet. We are collecting data on it. This is one of the reasons that participants in the clinical trial trials are being followed for another two years. This is something we really need to find out. And this is why you will hear people say that even with a vaccine, we need to maintain social distancing and wearing masks, together. Remember, it's not one or the other. And we need to keep using those precautions until we have the data on whether or not vaccinated people can transmit the virus.

[How long will immunity from these vaccines last?]
So let's talk a little bit about how long we can expect the immunity that the vaccine gives us to last. To begin to understand this, let's talk about what we know of other coronaviruses. When coronavirologists talk about immunity from natural coronavirus infections that we already know about, they talk in terms of years, not decades, as opposed to something like measles. Right? We get a measles series when we're young, and then we don't need it again.

That would be something that has immunity that lasts for decades. So for coronaviruses the natural immunity we see is shorter lasting than that. If I had to guess, I would say that we're probably looking at, at least a year for protection from the vaccines. But this is something that we're still collecting data for in the clinical trials. And every month that goes by, we will have more information about how long this immunity lasts. So the fact that that is unknown, as is whether or not a vaccinated person can transmit the virus, mean it's really important that even though vaccinated, we keep maintaining social distance and mask wearing until we have these data.

[If you recovered from COVID-19 should you get vaccinated?]
Okay, now, another important question that I've heard a lot is whether or not somebody who had COVID-19 and recovered should get a vaccine. And the answer to this is related to what we just talked about: the fact that we don't know how long immunity lasts. We don't know that information for natural infection either. And because we don't know how long somebody with a natural infection will be protected. It's important that people who have recovered from COVID-19 get the vaccine, and in fact, has been recommended by Dr. Fauci in one of his press conferences.

[Should pregnant women get the vaccine?]
Okay, so what about pregnant women and children? Should they take these vaccines? Currently, the opinion of the American College of Obstetricians and Gynecologists is that pregnant women should be given the choice to be vaccinated with these vaccines. And I agree with that, because messenger RNA are so short lived, they are not going to hang around the body. They're not going to make it to an embryo or fetus. So I don't see how these mRNA vaccines would be any riskier for pregnant women than for a non-pregnant woman. Obviously, the vaccines cannot be approved for pregnant women without clinical trial data. And thankfully, pregnant women are making the choice to get vaccinated, and they're going to be providing us with this data. Nursing mothers should also talk to their doctor and make a decision based on what they're comfortable with. But I feel the same about that, as I do with pregnant women. I don't see how mRNA from this vaccine would make it into breast milk. But again, if you're in a group for which we have no clinical trial data, then talk to your doctor and make a decision together.

[Should kids get these vaccines?]
All right, so what about kids? Should kids get these mRNA vaccines? Well, that's, that's a little bit trickier. Not only do we not have clinical trial data for children, younger than 16 in one of the trials. Although they have started trials in younger children now, but we won't have that data for a while. But anyway, so children can get infected with this right, and they can get sick, they can die. And in addition, they can experience a multisystem inflammatory syndrome. It's called MIS-C. And this is a really concerning syndrome. And there have been some deaths with it. We have no indication yet of why this happens in some children and not in others. One possibility is that during natural infection, the levels of the virus spike protein get really, really high. And that much spike protein causes this really dangerous, inflammatory response. We don't know that. But if that's the case, it's likely that the vaccine wouldn't result in the same levels of virus spike protein. So the exaggerated inflammatory response shouldn't happen. But again, we need data for this. Because of this concern, it's prudent to wait for the clinical trial data for kids. You know, discuss it with your pediatrician and see what's best for your family.

[Comparison between the Pfizer and Moderna mRNA vaccines]
Alright, now I'm going to get into a comparison between the Moderna and Pfizer vaccines. They're both messenger RNA, but there are some differences and I know people are curious. Okay, so they both require two shots. The Pfizer vaccine has 21 days between the first and second shot. And the Moderna vaccine requires 28 days between the first and second shot. The Pfizer vaccine was tested in people 16 and over, whereas the Moderna vaccine was only tested in adults 18 and over. Now, I know that people are curious, especially about the storage conditions. Because as we know, the Pfizer vaccine has some storage issues, it needs to be kept at minus 80 degrees Celsius, which is the kind of freezer that you have in laboratories, sometimes in hospitals, and it can last five days in a refrigerator before you have to throw it away. Now, that makes it really hard to get to places that don't have those kind of freezers available. It also means transporting it long distances, requires refrigerator and freezer cars, a lot of things many places just don't have. The Moderna vaccine, on the other hand, can be stored at minus 20 degrees Celsius, which is the temperature of a home freezer basically. And even better, the Moderna vaccine can stay in the refrigerator for up to 30 days. Now that allows transportation much easier, and storage in places that only have regular freezers. No doubt these limitations of the Pfizer vaccine are being used to decide where to send which vaccine.

So why are there differences in the storage conditions for these two mRNA vaccines? Well, as I mentioned early on, mRNA is very fragile. I mean, I swear it will degrade if you look at it wrong, and stabilizing the messenger RNA so that it could be an effective vaccine platform has been the problem for decades. Well, the scientists at Pfizer and the scientists at Moderna came up with solutions that worked and they are very similar, to stabilize the messenger RNA in the vaccine solution. These companies both add different combinations of fats, salts, and sugars. And these stabilize the messenger RNA and they also help the messenger RNA get into our cells. The differences between the two vaccines that result in the storage condition differences are just the combination of fats, salts and sugars that are included in the vaccine formulation. Now, you might have heard of polyethylene glycol or P-E-G, also called peg, being considered as a component of both vaccines that may be responsible for… for some of the allergic reactions we've seen. So what is peg? It’s polyethylene glycol and it is a poly ether compound used in many things, from industrial manufacturing to medicines. I mean, we use it a lot. In medicines, it's usually used as what is referred to as an excipient; or a compound that can stabilize the active ingredients in a medicine. And that's what it's used for in these vaccines. Actually, it's added to the fat component of the vaccines, which are lipids, and lipids create layers. And if you add peg to the lipids, it's a process called pegylation. So pegylated lipids are more stable, because their layers have more order to them because of the peg. So peg is very common in the products that we use. So it will be interesting to see what we learn as we gather more data on the allergic reactions.

The last point I wanted to bring up about messenger RNA vaccines is how easy and fast and cheap they are to produce. Unlike with other vaccine platforms like live virus or virus protein platforms, you don't have to mass produce the virus particles or virus proteins with mRNA vaccines. And that's because our cells produce the virus proteins for us using the messenger RNA. And even better than that, messenger RNA is much easier and cheaper to make than virus particles are proteins. So this vaccine success is a huge step forward. This is brilliant vaccine technology that will transform how we make vaccines in the future, and these scientists who made it possible are to be celebrated.

Well, that's it for my messenger RNA episode. I hope you join me next week when we talk about the other vaccine platforms that are in development for COVID-19.

Thanks for listening. Until next time, this is Dr. Heather Lander reminding you to keep it in perspective.

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