This episode features Natural Medicine Journal editorial board member and Covid-19 expert, Heather Zwickey, PhD. She answers our questions about mRNA technology, long-term immunity, and how to help enhance a patient's response to the vaccine. She also talks about Moderna's request to cut the dose in half and describes which patients may need to be careful regarding vaccine efficacy.
Editor's note: In this interview, Karolyn refers to mRNA as microRNA but she meant to say messenger RNA.
Approximate listening time: 16 minutes
About the Expert
Heather Zwickey, PhD, is a professor of immunology and chair of the Department of Health Sciences at the National University of Natural Medicine in Portland, Oregon. She launched the Helfgott Research Institute, which advances the science of natural medicine. Zwickey founded the school of graduate studies and developed masters programs in research, nutrition, and global health. Zwickey has received the Champion of Naturopathic Medicine Award from the American Association of Naturopathic Physicians. She currently leads a National Institutes of Health–funded clinical research training program focused on integrative medicine research and studies the gut-brain axis in neuroinflammation.
Karolyn Gazella: Nearly 2,700 people die every day of Covid-19. By the time we finish this short interview, it's likely that 30 more people will have died from this virus. This pandemic is clearly out of control. But hope is on the horizon in the forms of vaccines that use special micro RNA technology. Hello, I'm Karolyn Gazella, your host and the publisher of the Natural Medicine Journal. So the plan is to get enough people vaccinated so we can achieve herd immunity to hopefully stop the Covid-19 carnage, but many questions remain about these vaccines. Today I'm joined by our Covid-19 expert, immunologist and professor, Dr. Heather Zwickey. Dr. Zwickey, thanks for once again agreeing to tackle the tough questions.
Heather Zwickey, PhD: Absolutely. I'm glad you're willing to pose them.
Gazella: Yes, good. Well, as I mentioned, the new Covid-19 vaccines use micro RNA technology. How new is this technology? Can you give us a little background?
Zwickey: Sure. The technology isn't as new as it seems. Scientists have actually been working on DNA and mRNA vaccines since the 1990s, so it's been more than 20 years. Historically, they've been used in experimental settings, specifically working on cancer. The focus hasn't really been infectious disease because, well, we already have working vaccines for most of the major infectious diseases. So while it feels new to us in the general public because we haven't seen these vaccines before on the market, they actually have quite a bit of data behind them.
Gazella: Okay, good, good. That's great background. Now what's maybe the most confusing or misunderstood aspect about mRNA vaccines that practitioners may have?
Zwickey: I've heard a lot of misconceptions. Probably the biggest one has been that people are concerned that the mRNA could get into the nucleus and interfere with cellular DNA, and then be passed on for multiple generations. Now we know that doesn't happen. Actually, the mRNA doesn't get into the nucleus at all. It is transcribed in the cytoplasm of the cell, so it doesn't get into the nucleus. The second thing is that people have been concerned about fertility because they're concerned that the mRNA could get into eggs and sperm and the gonads. This also doesn't appear to happen. What's happening is when you inject the vaccine into the muscle, the majority of cells that take up the MRNA liposomes are actually macrophages, it's not even muscle cells. And the macrophages are short-lived once they take up this mRNA. So macrophages are designed to clear things from the body, and that's essentially what happens.
The mRNA is taken up, and then it's quickly transcribed by the macrophages, they help mount the immune response with the T-cells, and then the mRNA is destroyed, so it doesn't stick around, and it's not getting into germ cells. And then finally, people are worried about the ingredients, things like aluminum that are in some of our other vaccines. But I want to confirm that there is no heavy metal in any of the mRNA vaccines. The ingredients and specifically the mRNA and the lipids.
Gazella: Okay. Great. That's some great clarifications. So with vaccines in general, do they stop the spread of the virus?
Zwickey: Well, technically no. What vaccines do is reduce the symptom severity and the duration of infection. Because the infection is shorter, then people wind up being infectious for a much shorter window of time. And ultimately, that will stop the spread, although not immediately. And that's an important point because even if someone has been vaccinated, they could still get an infection and spread it, so it doesn't mean they're 100% safe. And it doesn't mean they need to stop wearing masks.
Gazella: So they could still get it and spread it. Can they also still get it and get sick?
Zwickey: What we're seeing from the data so far is that a small percentage of people do still get sick. It's less than 5%. So you can still have the vaccine and still get sick, it's just not very common.
Gazella: Okay. Another aspect is long-term immunity. So we know that vaccination generates antibodies. But do we know if those antibodies provide long-term immunity? I mean, how much do we know about long-term immunity when it comes to the mRNA vaccines?
Zwickey: Well, we don't know a whole lot about long-term immunity because these vaccine trials are only in the fourth month right now, so that's not long-term immunity. Keep in mind that the trials are designed to last 2 years. It's just that because of our emergency situation, we're reporting data early. Now you asked about antibodies, so let's talk about them for a minute. Antibodies are not as effective at long-term immunity as T-cells are. We measure antibodies because it's easy for us to do. They're in the blood and they can represent what the immune system is doing, but antibodies are always temporary. Even the longest-lived antibodies are only around for a couple of months. So in order to have good long-term immunity, we need vaccines that stimulate virus-specific T-cells. Now the data out of both Pfizer and Moderna vaccines that is published and available for public consumption have shown that they actually do get T-cell immunity with these vaccines, and that's a good sign for long-term immunity.
Gazella: Okay, perfect. So hot off the presses this past week, Moderna is now saying that they want to cut the vaccine in half to speed up the rollout and get more people vaccinated. Now I'm not a doctor, and I'm certainly not an immunologist, but to me, that doesn't really make sense. Now I know a lot needs to happen before this step is even taken. But what's your view on this idea?
Zwickey: Yeah, it's a really great point. If you look at the Phase 1 clinical data for the Moderna vaccine, it suggests that for people who are under 55, the half dose is actually as effective as the full dose. Now Moderna chose to make their vaccine with what we would call the current full dose because it worked also for people who were older than 55. But in the original Phase 1 studies, the researchers did a dose-escalation study. This means that they used a whole bunch of different doses and they looked at the effectiveness of the vaccine at many different doses, and there's actually a good immune response at several of the doses.
But since the folks who tend to not respond to the lower doses are the elderly, they chose to make the vaccine with a much larger dose so that the elderly would respond. So what they've proposed is that they could use a half dose for people who are between the ages of 18 and 55, and that would free up more doses. Frankly, I like the idea. However, the FDA didn't like their idea. They have said that it's going to take at least 2 months for them to review that data and decide whether that's a good decision or not. And I think it has to do with the public health aspect, that if you're rolling out the exact same vaccine in multiple doses, it's possible that you could have elderly people receiving the low dose just because mistakes will be made. And so I think that's one of their issues.
Gazella: Yeah, that would definitely be an issue. But even with the flu vaccine, there's different flu vaccines that are given to the elderly versus younger people. Correct?
Zwickey: Indeed, indeed. It can be done. It just requires a little bit more organization.
Gazella: I mean, it's fascinating. So when you're talking about half as much being effective, and that's really good news to hear, frankly, would you also get the second dose at the half dosage as well? Is that how the dosing trial, phase one trial, was performed?
Zwickey: It is how the phase one trial was performed. They still gave 2 doses, and the half dose for people under 55, and in fact, you could even go lower. The 30% dose was even effective for people under the age of 55.
Gazella: And how does this compare to the Pfizer? Do we have any of that dosing data with Pfizer? Is it a totally different animal?
Zwickey: Pfizer also did a dose-escalation study, and their half dose also works just as well as their full dose.
Gazella: Okay, cool. So switching gears a bit, and honestly, this next part of my questioning is really why I wanted to have you on the podcast. So there are many factors that can impact how effective a vaccine is on an individual patient basis. Now talk broadly. What are some of those factors that practitioners should be aware of that can in fact impact vaccine efficacy?
Zwickey: Yeah. So immune status of course is the biggest factor. And when we think about immune status, a lot of us are inclined to go, "Well, how healthy is that person?" Well, one of the biggest factors that affects immune status is whether or not people are on medications, especially immunosuppressive medications, so if they have autoimmune disease, or they've had a tissue transplant, or cancer, they're not going to have a very good response to a vaccine. But what we forget is that many, many medications are immunosuppressive. So if people are taking cardiovascular medication, their immune response will be less than someone who's not, so that's the first aspect.
Age-related immune decline is clearly also a consideration. We know that the older people are, the less likely they are to respond to a vaccine. We know that the health of the gut microbiome has a huge effect on whether or not people respond to vaccines. And that of course is also then going to be impacted by micronutrient status.
Gazella: Yeah. Let's dig into those because I actually was so fascinated by this subject. I did a search in the scientific literature, and I looked at zinc, vitamin A, vitamin C, vitamin D, and probiotics. And you mentioned the gut microbiome. I was surprised that the most compelling data showing enhanced vaccine efficacy is with probiotics in the gut microbiome status. I mean, actually with some of these micronutrients and these vitamins, it was mixed, based on what I found. So talk specifically about these. What's your view on these selected nutrients, and how nutrient status can impact vaccine efficacy?
Zwickey: Well, our first indication that nutrient status was impacting vaccine efficacy happened with vitamin A and measles. There was research in countries with low economic resources that showed that if kids didn't have a good vitamin A status, they didn't respond to measles vaccination. And as a result, even to this day, when we're vaccinating kids in countries with low economic resources, they're given a vitamin A tablet because otherwise, they just don't respond to the vaccine, so that's really where it started.
Now we all think of zinc as one of those micronutrients that affects the immune system, and indeed, it does. But if you're talking about a vaccination with or without zinc, there actually really isn't good data supporting that you're going to get a better response. Likewise, with vitamin C and vitamin D, we want those micronutrients to be at good levels in our body so that our immune system functions properly, but more doesn't necessarily mean more immune response. It's not a 1-to-1 dose-escalation sort of thing.
The big thing of course is the probiotics. And the probiotics are important because they're affecting the gut microbiome. But remember the microbiome and the immune system are reacting in the gut all the time. Seventy percent of your immune system, 70% to 80% of your immune system is in your gut, so if your gut is healthy and your gut is happy, it can respond to a vaccination. Probiotics appear to be effective because of the metabolites that are present. So probiotics, in addition to there being bacteria in a bottle of probiotics, those bacteria have undergone respiration, and they've eaten food and created metabolites. And it's actually the metabolites from the probiotics that look like they are impacting the immune status and improving vaccine function.
Gazella: That makes a lot of sense. And in some of the research, it also mentioned prebiotics. And we all know that prebiotics in the diet can create a healthy gut microbiome. Are prebiotics also on your radar?
Zwickey: Absolutely. And I think the thing that I like to remind people with prebiotics is that they aren't necessarily ... I mean, while all plants are prebiotics, your strongest prebiotics aren't necessarily the same plants you say are the healthiest. So we don't go straight for kale or that sort of thing. Prebiotics, we're really talking about leeks and onions and garlic and those foods that have the really long fibers because that's what your microbiome likes to feed on, artichoke, Jerusalem artichokes, sunchokes, all of those sorts of things.
Gazella: So from a practitioner standpoint, is the research compelling enough to say, "Well, if you have a patient with a compromised gut microbiome that you're working on, you're trying to shore up their gut, and you're trying to get them healthy in that manner," is it to say, continue to work in that direction before they get the vaccine? Or are we not quite there yet?
Zwickey: Oh, absolutely. We should be working in that direction before folks get vaccinated. And I think that's true for everyone. This is a great excuse, if you will, for all of us to pay attention to our lifestyle and our risk factors, and really get ourselves committing to becoming healthier.
Gazella: I would agree. And it certainly lends itself to being an expertise that the integrative practitioner, kind of a gap that they can fill in this area with their patient populations. At the end of the day, Dr. Zwickey, getting vaccinated is a personal decision, and I'm going to ask you point-blank. Will you be getting vaccinated?
Zwickey: I will. We've talked about this before. I believe I had Covid back in March before we were testing people under the age of 60. So I'm actually pretty confident in my immunological memory. However, I don't know if the quality of my immunity is above that 90% mark that these vaccines are getting. And I work in a medical school, where my students are being exposed to vulnerable populations. So if I balance my risk of getting Covid with the risk of vaccination, especially with these mRNAs, the risk of vaccination is lower for me, so I will get vaccinated.
Gazella: Great. Well, good. Well, thank you again for helping us out with this tough topic and for shedding some light on such an important, important topic. Thanks again for joining me, Dr. Zwickey.
Zwickey: Thanks for having me.
Gazella: I also want to remind our listeners that if you are new to the Natural Medicine Journal Podcast, you can find us everywhere and anywhere you listen to your podcasts. You can also find past episodes at naturalmedicinejournal.com. That's naturalmedicinejournal.com. There's a podcast tab. Just click on that tab and you'll find all of our past issues. Stay safe, everyone, and thanks for listening.