Your vaccine questions answered

Early on in the coronavirus pandemic, infectious diseases expert C Buddy Creech caught coronavirus, as did his wife and three children. Each family member was struck differently by the virus, some more severely than others. Creech wrote in an October 2020 essay published by Vanderbilt School of Medicine that his family’s varied experiences “illustrates the wide spectrum of disease caused by the virus.”

In the fight against Covid, masks are still relevant, says Creech, as is Remdesivir. Race has played a role in who is getting the vaccine. More white Americans are being vaccinated than people of colour, even as Blacks and Hispanics are still disproportionately affected by the virus.

As director of the Vanderbilt University Vaccine Research Program in Tennessee, Creech and his team have been working on ways to help alleviate racial disparities, but as he says, “We’ve got years of missteps, dating back 50 to 75 years ago, that we’ve got to recover from. And that just takes communication, it takes trust, it takes transparency.”

I spoke to Creech about what we’ve learned about the virus since the pandemic began, how to make vaccine access more equitable and why he describes this time as the dawn of a golden age of vaccinology.

Yvonne Bang: In an essay published in October 2020, you shared your experience contracting Covid in the early days of the pandemic. So much has changed in the year since you recovered. What are your thoughts about what has been accomplished in that time and what you know now about how the virus works?

Buddy Creech: I think one thing that we understand is that it’s not going away on its own. There were some who thought maybe this would go like the original Sars did in the early 2000s, where it threatened human health considerably and then, in large part, just sort of fizzled out. I think a lot of people hoped that would happen. It certainly didn’t.

The second thing is that we never historically have been able to prove that mask-wearing is something that has benefits outside of the healthcare system. We studied it for influenza and for other respiratory viruses, and I think that formed the basis of our public health stance very early in the pandemic, in February and early March. But then I think it became crystal clear that communities that took seriously these efforts of distancing and mask-wearing really had decreased disease. And if you look at the cadence of the pandemic over the year, you saw these rises and falls that often correlated with how compliant our local communities were with these basic measures.

Many people still have concerns about how quickly the Covid vaccines were developed. What factors sped up vaccine development?

The three categories are money, time and pride. We poured a terrific amount of resources into this from a financial standpoint. We provided funding to the research sites that needed to do these clinical trials. We provided risk mitigation to manufacturers, to industry partners here in pharma, to make vaccines without feeling like their profit lines were just going to get destroyed. It wasn’t just on them. We were funding the trials on a public level. We were buying vaccines even before they were proven to be effective. So, some of it was the financial investment.

The second is time, and that time issue is really important. For the last year, we eat, sleep, vaccinate — that is our rhythm. And it has been a really important year for Covid. Admittedly other diseases, other clinical trials, have taken a backseat, and that’s just the way it is. But it shows us what we can do when we hyperfocus on one pathogen or one disease. It’s interesting, and it might be a model that we want to pursue for other scourges of the globe.

The third one is one that I kind of jokingly say: pride. But it basically was a combined effort. When all of our noses are pointed in the same direction, we can really do some good things. Whether that’s Merck coming alongside and helping make the Johnson & Johnson vaccine, whether that’s Pfizer and BioNTech getting together and forging a collaboration.

I think the other piece is making available the really important basic science discoveries that have occurred in the last 20 years.

So, for instance, the story I like to tell with mRNA vaccines is that these didn’t happen quickly — it’s taken 20 years. It’s been 20 years since we learned that the spike protein is the most important part of the virus from an immune standpoint, and in fact, it’s the shape of the protein before the virus docks with your cells that we really need to make an immune response to.

You have already had Covid. Did you get vaccinated, and should other individuals who have already had Covid?

Yes, I think they should. I’ve been vaccinated. The variability in the robustness of the immune response after disease is really important. So, even in my own family, there were three of us, of our five, who had antibodies measured in our research laboratory. My daughter had next to no disease, maybe felt bad for a day or two, and her [antibody] level was four times normal. And then my wife, who was sick for about a week, flu-like illness, lost her sense of smell, she was 70 times, so hers was 7,000. Mine was 25,000, and I was the sickest of our group, having fever for over two weeks. So, we know that the severity of infection is correlated with the height of immune response.

So, just having a positive test doesn’t tell me much. What I think we need to be doing is: those who have had mild disease, they absolutely need to be vaccinated. We may get to the point where we realise that those with more substantial or more severe disease, maybe they only need one dose. But I still think a boost is really important, especially since we’re seeing these variants emerge that may require a higher number of circulating antibodies to be protective; and because we probably will see things — like transmission or asymptomatic infection — [that] are going to be prevented for longer when we have higher antibody tiers.

Are vaccines protecting people against Covid variants?

Yeah. We have indirect evidence in the clinical trials from Pfizer and Moderna studies because they were done prior to these variants really taking root. But serum from these individuals neutralise the virus in laboratory assays. Then, when we’ve seen them launched in the wild, we certainly are seeing decreases of disease activity even in those areas where variants are plentiful.

The Johnson & Johnson study gives us direct evidence, particularly for variants that are circulating in Brazil and the B.1.351 that’s circulating in South Africa. There was 100 per cent efficacy against Covid-related hospitalisation in death, even when that variant represented over 90 per cent of circulating strains. So, I think that gives us the most direct evidence that this particular vaccine construct, however it is delivered, whether it’s mRNA or viral vector, is going to protect against severe disease due to the variants.

The reason I think we’re having such success is that we are presenting to your body the genetic code corresponding to that spike protein, and your body is making that protein just like it would if it were infected by Covid, but we’re not letting it see the rest of the virus.

You think about other vaccines, where we have to grow them in chicken eggs or we have to make them in some sort of manufacturing facility in Michigan. This is different because, when we make them that way, we have to make sure that the protein is folded correctly; we’ve got to make sure that it’s pure; we’ve got to make sure that everything worked the way it was supposed to.

In this system, the mRNA and the viral vector systems, we’re giving our body the recipe; it’s going to make it because that’s what it does. So, if you will, the purity of the vaccine, it’s just a trim, lean way to tell your body, “I’m going to trick you for a few hours into thinking that you’re infected with this virus.” You may have some fevering, you’re probably going to have some heart pain and some feeling yucky for a day. Then it’s going to be over and because we gave you just the one target, you’re now going to be immune and you’re going to recover very quickly from those symptoms.

It’s a brilliant strategy, and I think that’s why I’ve called this time for us the dawn of a golden age of vaccinology because these are tools that are going to be used for a number of pathogens.

One of the things about children’s response to Covid is that their immune system is handling it better. Can you explain this?

Where children are really important is maybe in two or three areas. Number one, they don’t make, we don’t think, as much of that ACE2 receptor that serves as the docking station for the virus. They’re at less risk overall for disease, so that might be one of the reasons why there are different serums. In addition, they don’t have some of the underlying comorbidities, so they don’t have that chronic inflammation that might be the cause of some people’s immune systems just going haywire with Covid. Then third, they’re constantly seeing coronaviruses, since that’s the cause of probably 25 per cent to 30 per cent of the common cold. They’ve recently seen other coronaviruses and, therefore, they may have some pretty good immunity because of the fact that they’ve just seen them for the first time.

All of those factors may contribute to kids being less likely to have severe disease from Covid. Why that’s important is that, when we get the vaccine for children, we want to make sure we don’t disrupt the normal type of coronavirus immunity that happens through natural exposure to what typically is an easily controlled virus.

People of colour are receiving the vaccine at a much lower rate despite being disproportionately affected by the virus. How can we make vaccine distribution fairer for everyone?

I think we’re really working on this and it’s very challenging. We have a group here at Vanderbilt, led by Consuelo Wilkins, who is singularly dedicated to this right now because we want to make sure access to vaccine is not limited to those who have a very high healthcare literacy, or literacy about how to game a system in terms of how to get access. We really want vaccines to be able to go to those who are being disproportionally affected. That’s been largely in our Hispanic and our Black populations, for a variety of reasons that we don’t completely understand.

I think it’s challenging. One of the things we were very focused on during vaccine development was ensuring we had diversity within our clinical trial participants. And not merely racial and ethnic diversity, but socioeconomic diversity, diversity of medical problems, a lot of factors, because we want people to say, when they go sign up for a vaccine, “Someone a lot like me was involved in the clinical trial, and, therefore, I can have confidence that things are on the up and up.”

I think that’s really critical for us moving forward. I think we’ve got years of missteps, dating back 50 to 75 years ago, that we’ve got to recover from. And that just takes communication, it takes trust, it takes transparency, and it takes intentionality. And that’s what we’re trying to do locally, and I’ll tell you we’re really proud of the fact that in our phase three Moderna study, we recruited far fewer non-Hispanic white individuals than we typically would because we were trying to be very intentional about it.

What’s your opinion about reaching “herd immunity”? What percentage would that be of people vaccinated? And when might we reach that?

Yeah, we don’t know is the answer! We’re taking a lot of cues from smaller countries and smaller communities where vaccines are going very well, like Israel. And as we see those groups get to 40, 50, 60 per cent vaccination, I bet we’re going to see tremendous drops in that area. I think the other thing we can see is, if we can get a handle on how many of our 60+ and 70+year-olds are vaccinated, and then look at disease rate in those communities, I think that will also tell us a lot about the role of population immunity.

I would assume that it’s going to have to be more than 50 per cent to work. It might need to be somewhere around 70 or 80 per cent. But let’s keep in mind, our goal is not to keep everybody from getting infection — that may not be possible, it’s a respiratory virus, those are really tough. Our goal is to keep people out of the hospital and to prevent fatal cases of Covid. The overall disease rates are a little less important than hospitalisation rates, fatalities and complications of Covid.

I think what we’ve got to do is hyperfocus on those who are at highest risk of disease. That’s what we’ve been doing. And then I think we’ll see sustained decreases in disease activity. When that happens, we can steadily start to reopen things in a very profound way, not only for those who are vaccinated but also for those who are at lowest risk of complication.

Will this Covid become endemic, constantly circulating from year to year?

I personally do think it will. I think this virus is too good at being adapted to the human host and every indication would point to it maybe becoming our fifth circulating coronavirus. And again, if this virus only causes troubles the very first time you see it, that’s a pandemic we can answer. If it’s continuing to cause problems, that gets a little more challenging. But every indication is that this virus is going to be with us for a considerable amount of time, which is all the more reason to get vaccinated.   BY THE STAR