Since March bow-tied vaccine researcher Peter Hotez has worked to convey a scientist’s view of COVID-19 to everyday Americans. This week, he agreed to answer readers’ questions about vaccines.
Hotez is a professor and dean of the National School of Tropical Medicine at Baylor College of Medicine, and co-director of the Texas Children’s Hospital Center for Vaccine Development — where he and his team are working on a COVID-19 vaccine.
You were vaccinated yourself in mid-December?
I just got my second dose last night. [Laughs.] I’ve got my get-out-of-jail-free card.
How long does the vaccine take to work? You and your family were taking extreme precautions. Could you relax after the first does? Can you relax now?
Even after you get the second dose, we still don’t know if you can transmit asymptomatic infection. So until a high percentage of the population gets vaccinated, you still may need to take precautions.
So for instance, my wife and daughter don’t have their complete vaccine. That means if I go out or go to work, I could still bring home the virus. I think that probably doesn’t happen — that people who’ve been vaccinated carry the virus — but we don’t have the evidence base to be sure.
My big concern now is whether the nation and the state of Texas have put in place what we need to vaccinate our way out of this. We have not done a good job in the state of Texas of controlling COVID. We lead the nation — we’re either No. 1 or No. 2 — in deaths and the number of new cases per day.
We’re at this screaming high level. We’ve had close to 2 million confirmed cases in the state of Texas. And remember, that’s an underestimate by a factor of five. That means we’ve had roughly about a third of the state infected already. That’s why we have close to 30,000 deaths. We’re among the worst in the country.
There are reasons for that. We refused as a state to do the shutdowns — the lockdowns, as they like to call them — and there really hasn’t been much in the way of COVID containment. So we’re backed into a corner.
The only way we can get out of this and protect everyone is to get everyone vaccinated. I’m not confident we have that infrastructure in place. I mean, look at the numbers. We have roughly 30 million people in Texas. We have to get 75 to 80 percent vaccinated in order to interrupt transmission, according to studies we did with City University of New York last year. That means we have to vaccinate 24 million Texans, right? And if we want to do that over a period of eight months, that’s 3 million Texans a month. We’d have to vaccinate 100,000 people a day.
Some of the vaccines require two doses. So 100,000 Texans means roughly 150,000 immunizations a day.
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We’re not set up right now. We don’t have that infrastructure in place. We’re not going to do that with people calling around to H-E-B and Kroger’s and asking if they have vaccine for their mother or father, brother and sister.
The pharmacies are doing a good job. H-E-B is getting geared up. The hospitals are also. The health systems and the physicians’ offices are doing the best they can.
So it’s not as if they’re failing. It’s just that all those things together will not be sufficient to immunize 150,000 Texans a day.
That leads directly to a reader’s question. Jennifer Mathieu Blessington asks, “If you could choose, how would vaccine be distributed? I’ve heard people say that we need mass inoculation events at racetracks and stadiums, or to mobilize the National Guard. Do you think that kind of mobilization is a good idea?”
We have to look at what else can be done. Here in Houston, I think the City Health Department is creating community clinics for vaccination, and I visited the Bayou City Event Center site last Sunday. It was really well organized. I was impressed. But even that’s not going to be enough. We need a high-throughput mechanism.
Remember, we’ve never done this kind of scale for an adult vaccination. Historically, those big vaccination campaigns, like for polio, were for kids. We could use the school system for that. We don’t have that option with adults.
So yes, I think we have to put in additional large-scale infrastructure, preferably in an outdoor venue. And we have to train people to give the vaccine, because there can be serious allergic reactions. They’re rare — 1 in 100,000 or so — but they occur, and that’s a higher rate than for the influenza vaccine, so you want trained medical personnel to administer it.
Here in Houston we should look at opening up one of the sports venues, whether it’s AT&T, or Minute Maid and NRG, or some of the high school football stadiums. If we’re serious about vaccinating our way out of this pandemic, those are the kinds of things we have to put in place.
I’m a little surprised to find out that we’re only kind of approaching this now. I’m disappointed to learn that this wasn’t thought of earlier — or maybe it was, and I’m just not aware of it. We had nearly a year to think about vaccines.
Marrie Richards asks this: “It’s been argued that, in order to have enough vaccine to get more people immunized at least once, we should skip the booster shot. Is this a good idea?”
Several things have been proposed to stretch the vaccine supply: delaying the second shot; or cutting the dose in half for both the first shot and the booster; and even just giving a single shot, one and done.
The data is not robust enough to support implementing any of those. All those proposals are based on post hoc analysis of the Phase Three trials or looks at only Phase One data. To my mind, it just puts an added risk to the program without adequate evidence of benefits.
Let’s take the proposals one by one, starting with the single dose. All we know, right now, today, is that a single dose of the Pfizer vaccine will give you a modest level of protection for three weeks. It’s not very much protection. Looking at the virus neutralizing the antibody data, I would have said none, because it’s really between none and modest. So that proposal is a non-starter.
With delaying the dose, there’s the same risk. You’re just going to get people who get COVID.
Halving the dose is based on not a lot of data, from the early Phase One and Phase Two trials, that shows, “Yeah, there may be some merit to it, but it won’t be as good as the current vaccine.”
So my question is, why would you do that? All you would do is take a dysfunctional, unworkable vaccine infrastructure, which is what we have now, and instead of a least giving people hope that it’s delivering a good vaccine, you’d give them a crummy vaccine. A crummy vaccine on top of a crummy infrastructure is a non-starter. The answer’s no.
If you look at most of the people who are tossing out these ideas, they’re not vaccine scientists. They’re smart immunologists and infectious disease docs. They like the intellectual challenge of looking at the data and sort of speculating out loud. But from my perspective, it’s not a viable approach.
So what do you do? Well, one, you have to fix the infrastructure. And also, we’re going to need more vaccine.
This gets to the problem of the mRNA vaccines. We were never supposed to rely solely on the mRNA vaccines. It’s not a mature technology. It doesn’t have the capacity to do the job. We’ve known that for the whole year of 2020.
That was the whole rationale behind Operation Warp Speed: The mRNAs would be the first to get up, but then we would have later vaccines come along that are more robust in terms of production and the ability to vaccinate large numbers of people. That’s why you have the two adenovirus-based vaccines and the particle vaccines: They were they were supposed to be the worker bees on this. The mRNA was to get started, and then the others would follow it.
Our lab has a recombinant protein vaccine, and we’re scaling up to a billion doses. If the U.S. needs vaccine, you could bring our vaccine in from India, to do this. But don’t play games with the mRNA vaccine.
Not only does the proposal fail for scientific scientific reasons, it’ll also undermine public confidence, and a lot of the public is already skittish. If they see our leaders monkeying around with doses and intervals and things like that, the whole thing will fall apart. The people who are touting this idea are oblivious to public perception around vaccines. They don’t really understand how quickly a vaccine can be voted off the island.
An anonymous readers asks, “What are the risks of taking a vaccine prior to getting pregnant or receiving the vaccine while you’re pregnant? Since the mRNA vaccines deal with genetic material, are there any risks to the baby?”
Because the Phase Three trials are so large, even though they excluded women who knew they were pregnant, a number of women actually got pregnant during the trials. They’re being followed, and so far there are no adverse outcomes that we’ve heard about.
So you have to balance that against the known risk of getting COVID if you’re pregnant. The morbidity/mortality among pregnant women is really high. So if my daughter were pregnant right now, with this screaming level of COVID-19 transmission, I would want her to get vaccinated.
The American College of Obstetrics and Gynecology has basically said that: that the risks of getting COVID while pregnant far outweigh anything we’ve seen from the vaccine. The ACOG, the American College of Obstetrics and Gynecology and I think also the Maternal Fetal Medicine Society have also come out with a similar type of statement: Get vaccinated.
So have that discussion with your obstetrician.
Now, about the RNA vaccines: RNA isn’t going into the nucleus of the cell. The way an mRNA vaccines work is, it gets taken up by the cell in the cytoplasm. Remember cytoplasm? You had to learn about it in high school biology when you were learning about the nucleus. This is why you had to learn it.
The mRNA goes into the cytoplasm. There it’s made into protein. It doesn’t go into the nucleus, and it doesn’t get incorporated into DNA. There’s no genetic risk to the baby.
One of the big, fake anti-vaccine tenets out there is that the vaccine is causing genetically modified humans. It’s not. That’s all BS.
Randy Pace asks, “Will current vaccines work for the new strains of the coronavirus?”
That’s being studied now. For instance, our lab is testing our vaccine for that now in collaboration with a group at Duke University, where they have all of these various viruses or pseudo-viruses.
So yes, we have to confirm this, but I think the vaccines will work. Most of the mutations in those variants are not in the business end that the vaccines address — the receptor binding domain on the coronavirus’s spike protein.
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But we need to continue to monitor for variations. Even though these particular variants will probably be okay, eventually a variant may emerge — in a year, two years, or three years or 10 years from now — that can escape the vaccines. That has to be monitored.
I’m profoundly disappointed that we’re not really looking for variants in the U.S. The CDC program for that, like so many things this past year, has underperformed: The U.S. has sequenced only 50,000 virus genomes. In the UK, they’ve already done 200,000. Here we should have completed between a million and 10 million virus genome sequences.
The U.S. has that capacity. There’s no greater genome sequencing capacity in the world. We have the New York Genome Center, and the Broad Institute of MIT and Harvard. Here in Houston, Baylor College of Medicine is a national resource for genomic sequencing, with a lab headed by Richard Gibbs; it’s one of the premier genomic centers in the world. And Methodist has a lot of capacity. Plus there’s the University of Washington; and Washington University in St. Louis; and the Stanford genome center.
We should have a government-supported program in place so those robotic sequences are running day and night. We should have 10 million virus genome sequences. That’s not even that much: It’s the equivalent to a couple or just a handful of human genomes. We do that all the time. It’s not even that hard.
As a nation, we again have come up small in terms of public health response.
And it’s probably not only the UK and South African variants. It wouldn’t surprise me at all if we have two or three similar variants that are homegrown here in the U.S. We’re just not looking.
So should we assume that there are faster-spreading variants right here in Houston? That we don’t know about them because we’re just not looking?
That’s right. Actually, the Methodist group early on found one mutation — a Gly614 amino acid replacement in spike protein — that they thought was outcompeting the other variants and so may be more highly transmissible.
These genetic variations happen all the time. So far, it’s not affecting vaccine development. And so far, knock on wood, it’s not affecting severity of illness. But this virus is still spreading like wildfire — a quarter or a third of the population of Texas has already been infected — and there’s no end in sight. As long as it’s spreading, the mutations will just keep on going.
Marrie Richards also asks, “What caused the SARS-1 coronavirus to peter out? Was it a mutation?”
The original SARS was a bit different. One, if you got it, you were sick. There was no asymptomatic spread. So if you were sick, you were not going to bars and concerts or in school. You went right to bed. You were either at home very sick or in a hospital. That helped limit the spread.
The other piece to this is, the SARS-1 virus did not have a phase where there’s a lot of virus replication in the nose and the mouth. That’s unlike this one. With this one, we’re shedding a lot of virus.
Those two simple differences are responsible for what, in the absence of a U.S. public-health response, has become a catastrophe. With the current coronavirus, SARS-CoV-2, you have the nightmare scenario where you have two different populations: one population without symptoms, shedding a lot of viruses as they speak or talk or sing; and another going into intensive care units very sick.
And this is a catastrophe. We’re looking at close to 30,000 deaths in the state of Texas. Let me put that in perspective. The number of Texans who died fighting in World War II was around 20,000. The number of Texas lives lost in the Civil War, depending on which historian you read, was between 3,000 and 20,000. The Galveston hurricane of 1900 killed around 8,000. The Texas revolution — I should have known this, but I had to look it up — was 700 Texans, according to some estimates. We are looking at arguably the worst catastrophe in the history of our state, based just on what happened in 2020, and still with no end in sight.
Why am I saying this in such a strong way? I’m worried people don’t feel the urgency to get vaccinated. And I’m worried that our elected leaders are not doing everything they can to get Texans vaccinated. Every time a journalist talks to an elected leader, the first question they need to ask is, “What are you doing to vaccinate people in our state?”
I don’t want to hear about crummy ideologies. I want to hear what our elected leaders are doing to vaccinate people and halt the death toll.
That 30,000 is just the beginning. It will continue tomorrow. And it is the responsibility of every elected leader and every government official in the state of Texas to make this their No. 1 priority.
Right now it’s not. That gets me mad.
A lot of people who are allergic to pork or shellfish are asking whether it’s safe for them to be vaccinated. What’s your advice? What would you want them to think about?
I have a severe shellfish allergy: I’m allergic to shrimp. I took the vaccine. It was fine.
It doesn’t look like just any allergy will cause a severe reaction. You have to be allergic to the specific components in the vaccine. And we don’t really know what that piece is.
There’s a hypothesis being investigated. To stabilize the lipid coating around the RNA for the mRNA vaccine, they use something called PEG, polyethylene glycol. PEG is used in food additives and things like that, and polyethylene glycol allergy is a rare but known thing. It could be that that mRNA vaccine is unmasking the PEG allergy.
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But whether or not that’s what it is, we don’t know. So if you know you have a PEG allergy, or if you see something that’s in the vaccine that you’re allergic to, don’t get it.
Otherwise, go ahead. Or at least have a conversation with your allergist.
Olga Luisa Dentzien-Keller asks about the vaccines’ possible paradoxical effects. There was some thought early on that a vaccine for this virus might actually make the response to the disease worse for some people. Do we have enough data to know whether that’s happening?
There can be a problem called “immune enhancement” — it’s a real problem with some viruses — but we haven’t seen it with this vaccine. I was part of an NIH working group that looked into it. We’ve written a paper published in Science Translational Medicine.
I was the one who called attention to the possibility in a congressional hearing back in March last year. We saw immune enhancement with the RSV vaccine in the 1960s, and we’d seen it with some of the rodent models of SARS-1, especially with some of the whole-virus vaccines. That was what got me worried.
But we did look into it, and so far it’s not an issue. That doesn’t mean it can’t occur later on, but we have a monitoring system in place.
What the anti-vaxxers do is, they keep replaying and replaying my Congressional testimony from March. They say that I’m backtracking. But I’m not backtracking.
I said then that I was worried about it, and that we needed to look for it. We looked for it. We didn’t find it. That’s called science. That’s good science. The scientific method is very powerful.
Nancy Higgs asks, “How is your lab’s vaccine coming along?”
Thanks for asking. It looks great. My science partner, Maria Elena Bottazzi, and I are on Zoom calls all the time. It’s now being scaled up for production in India. It’s gone through Phase One and will soon go into Phase Two clinical trials with Biological E in India, and now we also have expressions of interest from other countries as well.
We just got the announcement that CEPI is supporting it, which is a nice sign of endorsement. CEPI — the Coalition for Epidemic Preparedness Innovations — is the big international mechanism. It’s part of a consortium with the Gates Foundation and the World Health Organization in Gavi, The Vaccine Alliance, that’s now supporting our vaccine as well. I’m very excited about that.
The one thing I would like to see is if we can find a path to bring this into the United States as well because it’s an older technology. It’s the same technology used for the hepatitis B vaccine. The reason that’s relevant is, that’s been given to kids for decades with a great safety record. So if we could get the right industrial partner, I’d love to bring this into the U.S. as a pediatric vaccine.
Speaking of kids and vaccines, Liana Silva asks, “Could you explain how a vaccine trial with children would work?”
They would initially go through what’s called “step-down studies.” After testing adults, they’d gradually step down the age of the people they test the vaccine on, starting with adolescent kids, under 16 — showing that it’s safe for them, making certain you’re getting adequate levels of virus-neutralizing antibody, and possibly even doing protection studies as well, comparing the vaccine to placebo.
After that, assuming that all goes well, you do the younger kids.
The only difference may be that, at some point, we’re going to look at correlates of protection — meaning that once you get a certain level of virus neutralizing antibodies and a type of T cell response, you may not have to do the whole clinical trial. I don’t think that we’re there yet.
It would be nice have that answer before the start of the school year in the fall of 2021. If we can get the kids vaccinated as well by then, that would even be better.
The good news is, now we’ll be able to protect the schoolteachers and the bus drivers and the parents. That’s been my big worry, and vaccinating adults will take that off the table. But there are kids who do still get sick, so if we can get them vaccinated, that would even be better.
What else should we be thinking about? What should we watch for?
The next big milestones, other than getting more and more people vaccinated, will be getting some of these other vaccines up. The adenovirus-based vaccines, I think those will be next — the Johnson & Johnson, the AstraZeneca-Oxford, which is already now being used in the UK.
I’d like to see those vaccines in the U.S. They’re a little more robust in terms of production, and you can make a lot more of them. They only need simple refrigeration. So that one we’ve got to do.
My big worry is that, as a nation, we’re backed into a corner. We failed on everything. We failed on the diagnostic testing. We failed genomic sequencing, We failed to halt the entry of the virus from Europe into New York. We failed to halt the Southern surge across the Southern states. We failed to halt this big fall mammoth fall surge.
U.S. strategy always came down to the same thing: “Vaccines are coming.” That’s all we have left, our last arrow, and we’ve got to shoot that one straight. If we don’t, it’s catastrophe — and we’re already having a lot of missteps in the beginning.
Not so much here in Houston: The mayor and county judge have put together a good program, but it needs to be scaled up. And I’m worried for our state.
This interview has been edited for length and clarity.
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