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Research and Innovation

Vaccine Q&A: Safety, Skepticism and How Long Protection Will Last

man receiving vaccination
Image credit: SELF Magazine. Shared under a Creative Commons license. Click for more information.

In this post, we focus on vaccine safety; some of the reasons people are hesitant to get vaccinated; the difference between preventing infection and preventing sickness; and how long a vaccine may protect against COVID-19.

To address those questions, we spoke with Matt Koci, a virologist and immunologist whose work focuses on host-microbe interactions in birds. Koci is a professor in NC State’s Prestage Department of Poultry Science.

This post is part of a series of Q&As in which NC State experts address questions about the vaccines on issues ranging from safety to manufacturing to how the vaccines will be distributed.

The Abstract: Given how quickly the vaccines were developed and tested, are you concerned about safety?

Matt Koci: I’m not concerned with anything I’ve seen so far. Looking at the data the FDA has released (not just the company press releases), yes, these vaccines went from zero to being injected into peoples’ arms in less than a year. Yes, most vaccines take 10 years or more to come to market. But no one cut corners. These vaccines have been tested as rigorously as they could be in the time allowed. In many respects, these vaccines will be the most scrutinized in human history, as all the world’s scientists are scouring through the data.

For example, when Oxford/AstraZeneca released data on its vaccine, even though the results looked good, the scientific community said, “Wait, those numbers don’t quite make sense.” In response, Oxford/AstraZeneca said, “You know what, we’ll do it one more time to make sure.”

We need these vaccines, but the world’s infectious disease scientists also know we need vaccines, period. The last thing we need is to get this wrong and give the anti-science/anti-vaccine groups more ammunition. That could be the end of one of the greatest human inventions.

COVID testing site. Photo credit: Jakayla Toney.

We also need to be clear about what is a negative side effect. A lot of people complain that they get “flu-like” symptoms from the flu shot. That’s one of the most common reasons people give for not getting their flu shot each year. Feeling a little run down for a day or two is not a severe reaction. That’s actually our immune system working. Feeling a little tired and a sore arm for 24 to 48 hours is a small price to pay to prevent 7 to 21 days of fever, cough, possible hospitalization or worse.

So far there are no signs of major adverse reactions. But people need to keep in mind there is a possibility that some of the vaccines might end up causing some issues for some people. So far, 30,000 people have taken each of the vaccines that are in phase 3 trials, and there have been no major bad reactions that can be linked to the vaccine. But we’re going to be vaccinating billions of people.

On the one hand, COVID-19 can kill 1 to 4% of those it infects. On the other hand, right now we’re looking at zero deaths [from COVID-19 vaccines]….From a big picture, public health perspective, I’ll take that trade-off any day.

The more people we vaccinate, the greater the chances we end up with some people with negative reactions. That doesn’t mean the vaccines aren’t safe, or that corners were cut. It is a risk/reward trade-off. On the one hand, COVID-19 is a disease that can kill 1 to 4% of those it infects, and it likely will infect 75 to 100% of the world’s population. So, we’re talking about 50 to 280 million deaths worldwide – not to mention impacts such as long-term health effects or the medical debt facing survivors in the U.S. On the other hand, right now we’re looking at zero out of 30,000 vaccinations ending in death or any side effects as severe as long-hauler syndrome. From a big picture, public health perspective, I’ll take that trade-off any day.

So if/when reports of negative reactions start to get reported, the media need to keep them in perspective. We have already seen some of this with reports out of the U.K. of a few people who had what appears to be allergic reactions to the virus. Based on the reports, it’s hard to figure out how many actually had a negative reaction out of how many shots delivered, but these types of reactions are rare and not unexpected. Looking at data from the clinical trials, 0.63% of the people who got the mRNA vaccine reported having any kind of allergic reaction, which is only slightly higher than the 0.51% of people who reported similar reactions after getting the placebo.

I’ll also point out that Operation Warp Speed’s investment in different types of vaccines accounts for these issues. We know some people may not be able to take some vaccines based on how they are made. If someone is at risk of an allergic reaction to one type of vaccine, they should be able to get safely vaccinated using one of the other vaccines that will be released in 2021.

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TA: Why are so many people already saying they won’t take the vaccine?

Koci: Different people have different reasons. Some have religious beliefs that forbid them from using modern medicine. For some, like African-Americans, it’s not so much a distrust of vaccines as it is a historical (and justifiable) general distrust of the medical establishment that bio-medicine has not done enough to address. For others, it’s rooted in a long-since discredited report of a link between vaccines and autism.

The truth is that over the past 20 years we’ve seen the numbers of people expressing concern and distrust of vaccines increase to dangerous levels. One reason for that is a vocal group of people who have made a lot of money convincing the public that vaccines aren’t safe, as well as active disinformation campaigns by foreign states. Unfortunately, most of us in science didn’t take these threats as seriously as we should have, quietly kept doing our work and did not engage in this debate.

So let me be clear. Vaccines are safe. There is no link to autism. This has been one of the most studied hypotheses in modern science and there is no evidence to support the idea. Some number of people may have negative side effects. No one wants to minimize those effects, but they occur at rates of one out of hundreds of thousands or millions of doses given. That’s similar to the odds of getting struck by lightning in a given year (which is 1 in 500,000).

Let me be clear. Vaccines are safe.

That said, a lot of parents who weren’t sure what to believe have used the risk/reward idea to decide that it wasn’t worth the risk. They said to themselves “I didn’t have the measles as a kid, I don’t know anyone who had the measles.” So they conclude the risk of getting the measles is lower than their perceived risk of a negative reaction to the vaccine, based on all the noise on social media. So they conclude that what’s best for their child is to not take the vaccine.

However, the reason they didn’t get the measles or know anyone who did, is because of the vaccine. If enough people in a community are immune to a disease it can end up protecting those in the community who aren’t immune. That’s what you’ve heard on the news as “herd immunity.” Herd immunity is what protects infants too young to get vaccinated, as well as others who may have allergies or other medical conditions that prevent them from taking the vaccine. The idea is that the herd protects the most vulnerable in the group.

If one or two people in a community make the decision not to take the vaccine it’s probably okay. But as the percentage of people in the community who refuse vaccination increases, eventually herd immunity breaks down. When that happens everyone who isn’t immune will get sick. We’ve seen this happen multiple times all across the globe over the past 20 years. Diseases that we thought were eradicated from some countries have returned because some communities have stopped using vaccines. Think of it like a crowded community pool. You might decide it’s no big deal to pee in the pool. With all that water to dilute it out, no one will notice. But you don’t need that many people to make the same decision before we’re all swimming in pee.

Photo credit: Chris Barbalis.

TA: A lot of the people who say they aren’t going to get the vaccine say we’ll get herd immunity naturally, are they wrong?

Koci: Yes! They couldn’t be more wrong. Nature doesn’t work like that.

Smallpox, chickenpox, influenza, measles, polio – all these diseases existed for hundreds if not thousands of years in humans, but they never went away because of herd immunity until we had vaccines. If herd immunity worked the way some of these people suggest, once a disease burned through a population it would be gone forever. Viruses don’t do that. Not everyone a sick person comes in contact with will get the virus. It literally might be as simple as which way the wind was blowing that day as to why one person got it and others didn’t. But that means next week, next month, or next year those people are still susceptible, so the virus can return and infect them. Year after year after year.

Most estimates suggest we need between 70% and 80% of the population to have immunity to see the effects of herd immunity.

Vaccines make it so that everyone (or as close as we can get) in the population is protected at the same time. So there are no people for the virus to survive in. When that happens the virus goes away.

TA: So what percentage of people do we need to get the vaccine to get herd immunity against COVID-19?

Koci: The honest answer is we don’t know. But based on other viruses that spread like SARS-CoV-2, most estimates suggest we need between 70% and 80% of the population to have immunity to see the effects of herd immunity. However, that depends on how effective the vaccines are, and whether they protect against infection or if they only protect people from getting sick.

TA: What do you mean by protect against infection versus protecting people from getting sick? Aren’t those the same thing?

Koci: We hope so, and that’s the ultimate goal, but the primary goal is to save lives and keep people out of the hospital. So initially any good vaccine will do at least that. But that could mean that the virus still gets inside you and replicates, it just doesn’t make you sick. If this is what happens you might not know you’re infected and you may still be able to spread the virus to other people.

Some vaccines drive an immune response that won’t even let the virus get started. If this is the case then those who are vaccinated will be protected from disease AND they won’t be able to spread the virus either.

Photo credit: Artem Podrez.

We don’t know yet if the COVID-19 vaccines just protect against disease (meaning they keep you from having the symptoms of COVID-19), or if they help prevent spread too. Given what data we’ve seen so far, I would guess they will help with spread, but we need more time and more data to have a better sense of this.

TA: You also said depending on how effective they are. What do you mean by that?

Koci: What percentage of people who got the vaccine are actually protected? This is biology, nothing works 100% of the time. In fact, most vaccines are only between 50 to 80% effective. That means only 50 to 80% of the people who get vaccinated actually end up with protection. The lower the percent effectiveness is, the more people you need to vaccinate to actually get herd immunity. If you need immunity in 70% of the population to get herd immunity, and a vaccine is only 75% effective you need to vaccinate over 934,000 out of 1 million people.

Reports from the phase 3 trials of the Moderna and Pfizer vaccines suggest 90 to 95% effectiveness. That’s fantastic. That’s way better than anyone would have thought nine months ago.

The next pandemic might not be so easy to vaccinate our way out of.

We really don’t know for sure all the factors that determine a vaccine’s effectiveness, but we got really lucky with this virus. There are lots of diseases that we’ve been trying to make vaccines against for decades and either they aren’t effective, or they come with too many side effects.

I’m glad this has worked out so well, but people really need to appreciate the fact that this was luck. The next pandemic might not be so easy to vaccinate our way out of.

TA: You said not everyone who gets the vaccine will be protected. But what about those who do end up with protection. How long will that last? On the news they say people who have recovered from the virus only have immunity for a few months. Will it be the same with the vaccine? How often will we need to get vaccinated?

Koci: First, it’s important to remember we first recognized this virus was in the U.S. in late January of 2020. It was completely unknown to science before December 2019. So we are still learning. Right now, it still isn’t clear how long immunity lasts following infection. It seems like most people have antibodies for a few months after they recover. Other people have them for longer. Regardless, while there have been a handful of reports of reinfections, we aren’t seeing a lot of reinfections. This means that even without antibodies other parts of your immune system may still be providing protection.

I don’t expect we’ll need to get revaccinated every three months, but only time will tell.

It’s also pretty clear that this virus makes some people’s immune systems behave in weird ways. In fact, the cases that require longer hospital stays seem to be because of an overly aggressive immune response. This may be why the protection you get after an infection is short-lived.

While we don’t know for sure, the vaccine probably won’t have that same issue. During the infection, all the things the virus is doing to the body seems to exhaust the immune system. The vaccine doesn’t cause this immune exhaustion. It is just some of the viral proteins presented to the immune system in a way that ensures the immune system can do its job. I expect that immunity from the vaccine will end up being better than immunity from infection. I don’t expect we’ll need to get revaccinated every three months, but only time will tell.

However, if the vaccine only protects against disease, and not against infection, we could end up with a situation where one of two things might happen. Maybe both. First, if we can still be infected but not get sick, this allows the virus to replicate in people undetected and eventually it could evolve in a way that the vaccine no longer works against it. If that happens, we’ll need a new vaccine. This would be similar to how we need a new flu vaccine every year, but not exactly the same process.

The other thing that could happen is like what happens with the tetanus vaccine. When you get the tetanus vaccine it’s good for 10 years, unless you’ve had a puncture wound that likely exposed you to the bacteria that makes the tetanus toxin. The vaccine drives your immune system to make antibodies against the tetanus toxin. But the bacteria makes a lot more proteins than just the toxin. When exposed to bacteria, your immune system then starts to make other antibodies besides the ones that protect you from the toxin. So you need to get another booster to remind your immune system what to focus on.

We might find out that the vaccine produces good, long-lasting protective antibodies against COVID-19. But that if you get infected a few times, the protective response may get diluted and a boost every so often might be helpful. We really don’t know.

TA: So there are several vaccines being talked about. Which one will you take?

Koci: The first one with emergency use authorization that is made available to me.

I don’t have a lot of good things to say about how the U.S. has handled this pandemic, but the strategy behind operation Warp Speed was smart. They backed several different vaccines, each representing a different vaccine technology. Since we didn’t know what was going to work, this made the most sense to ensure something worked.

The news has recently started a lot of noise about how the U.S. government turned down an offer from Pfizer to buy 100 million does in July. Again, the U.S. did a lot of things wrong during this response, and while today that looks like a stupid decision, in July we didn’t have enough data to know whose vaccine would work. The U.S. had already invested in Moderna’s vaccine, which is the same type of vaccine. So would I want those 100 million doses today? Absolutely. Would I have made the same decision the Operation Warp Speed group did in July? Almost certainly.