COVID-19 has become such a huge problem in the world that the race to find a vaccine against it is one of the most urgent public health challenges. Joining Dr. Diane Hamilton on today’s episode is Dr. Jerome Kim, the Director General for the International Vaccine Institute. Dr. Kim is an international expert on the evaluation and development of vaccines. He paints a picture of what’s going on with the development of the COVID-19 vaccine, highlighting the things we have to worry about in terms of that commitment to safety and efficacy.
I’m so glad you joined us because we have Jerome Kim. He is the Director-General of the International Vaccine Institute. He is an international expert on vaccines. We’re going to learn all about COVID-19 vaccines and what to expect. This is going to be a fascinating show.
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COVID-19 Vaccine: The Race For The Cure With Dr. Jerome Kim
I am here with Dr. Jerome Kim, who is the Director-General of the International Vaccine Institute, IVI, and an International Expert on the evaluation and development of vaccines. It’s nice to have you here, Dr. Kim.
My pleasure, Diane.
I was looking forward to this because we were introduced through our mutual friend, Rich Lofgren. I know you’re doing some interesting work in the area of looking at vaccines. I know COVID-19 is such a huge problem in the world. You’ve done work with the cholera vaccine. I was looking at the list of things. Before I give too much information, I’d like to hear from you about what you’ve worked on and how you got to this level.
It’s a long story. It’s a wonderful thing when the military will pay for medical school, and they did that. I was working on HIV at Duke and I thought I was going to go on and do faculty stuff. When I got my first grant, I wrote back to the Air Force and said, “Can I have a further deferment?” It was the start of the Gulf War. They said, “Wait a second. Where are you and why aren’t you in the Air Force?” Before I knew it, I was assigned to the Walter Reed Army Institute of Research, working for a guy named Bob Redfield. He’s the Director of CDC in 2020, doing HIV vaccine research. Right after that, Bob left. I left with him to go to the University of Maryland. Eventually, Debbie Birx invited me back into the army to work on the HIV vaccine. I go back a long way with them.
At the end of twenty years, after having done a phase three trial in Thailand that was the first and, at this point still, the only crowd that showed an HIV vaccine could protect against infection, I was eligible to retire. A job at IVI opened up. IVI works on everything but HIV. It was a perfect way to complement an interest that I had in understanding how other vaccines are developed. The beauty of IVI is that it’s an international organization. It’s a little odd, like the United Nations or WHO, but it’s the only international organization that develops vaccines. Rather than publish papers in science, nature, and cells, we focus on getting a vaccine from our laboratory through all the stages of testing. We transfer it to a company that can make it. We help the company, usually with funding from the Gates Foundation or Korea or Sweden or India, one of our state funders. We get it approved. The World Health Organization approves it. It’s eligible for purchase by UN organizations.
The oral cholera vaccine developed at IVI is 80% to 90% of the current stockpile. We don’t benefit from it but we’ve made a vaccine that the world benefits from. In 2020, we have a typhoid vaccine that’s in late phase three. We’re also working on other vaccines. We’re trying to figure out what the next vaccine will be. Our model is to identify a disease that’s a big problem in developing countries, learn how to make a vaccine that will work against it, work with funders and companies to make a vaccine, prove that it works, get it tested, approved, and then make sure that countries have it available to use. COVID is a lot like that.
I’m trying to decide which way I want to go first because there’s so much out there. Having worked in pharmaceutical sales, I dealt more with bacteria than viruses. I sold antibiotics and many different drugs in the past. It was challenging. At one point, I sold Cipro and those types of drugs. One of the hardest things to learn is all the pathogen names and all the things that go along with it. I actually ended up with meningitis later. I had viral meningitis and not bacterial meningitis, which I eventually heard was a good thing. In our minds, we think viruses are almost worse than bacteria because we have these medications for bacterial infections. On viruses, you don’t hear many helpful solutions. When I had meningitis, they told me that the bacteria left behind much worse remnants. That was why it was dangerous. It was good that I had viral meningitis instead of the other. A lot of people are confused between the virus and the bacteria. Why are we able to get some of these bacterial medications? Why is it hard to get anything to cure a virus? Why is it difficult?
That’s a great question. The thing about viruses is that one famous scientist calls them a piece of bad news wrapped up in protein. Bacteria are different from us. They have their own machinery inside of them and some particular ways that they have to reproduce. In other words, grow. There are particular things that are bacteria-specific about the way they make proteins or the way they make the outer coat. The fact that that is different makes it possible to target. Antibiotics will target different parts of the bacterium. Some of them will affect the outer cell wall of the vector, like the penicillins and cephalosporins. Others will target the little machine inside the bacterium that makes a protein called the ribosome, different from the human ribosome. You can give a bacterium something that stops their ribosome and it won’t harm the human ribosome, which is great.
The problem with viruses is that they’re a little bit incomplete. They need to grow inside one of our cells. They almost take over some of the human cellular machinery. That makes them hard to target sometimes because we can’t just knock out the human ribosome that makes proteins to stop the virus. When we do that, we’ll stop the human ribosomes elsewhere in the body. What we have to do is look for things that the virus has. For instance, with HIV, there’s something called reverse transcriptase. It turns the RNA from the HIV virus into DNA, which then becomes a part of us. We can target that reverse transcriptase because it doesn’t have a human homologue. There’s not a similar protein in humans. We can make all these drugs against the reverse transcriptase. That’s how the first effective therapies against HIV were developed. Viruses are a little different. It’s still possible to target them but it’s a little more difficult.
My husband is a physician. He was talking to me about when they created the polio vaccine to radically eradicate polio. They were in a hurry and they got some batches that weren’t complete yet. I’m thinking about that with COVID and what we’re working on now. He told me that they gave some of them to people that didn’t have the dead version. They had a live version of polio. People got polio. First of all, is that a true story? Is that something we’re going to have to worry about with COVID? Tell me a little bit about what’s going on with COVID and the worries and the things that we have to think about?IVI is the only international organization that actually develops vaccines. Click To Tweet
It is a true story, The Cutter Incident. We’ve evolved a lot in terms of vaccine manufacturing and vaccine safety. In those days, the poliovirus vaccine was brand new. At that point, we didn’t have many vaccines against viruses. If you think about it, the influenza vaccine was tested near the end of World War II. We’ve had smallpox but that was a chance discovery, at that point, maybe about 150 years before. It was a related virus called cowpox. Edward Jenner found it. Lo and behold, milkmaids didn’t get smallpox. Why? Because they were exposed to cowpox. Cowpox protected them. He turned it into a vaccine. That was an amazing discovery.
Between then and the development of the next set of effective antiviral vaccines was a long time. Finally, we learned how to grow these viruses in what we call a cell culture. We could grow them in the test tube. Once you could grow them, you could kill them. The first vaccines were just growing a virus, killing it, and injecting it. That’s essentially what they did with the Salk polio vaccine. Salk grew it in cells, inactivated it, and injected it. The problem with that is if you’re not following high standards for quality, occasionally a batch gets through that’s not completely killed. That’s back in the 1950s.
We’ve come a long way since then. There are now international standards for manufacturing quality called GMP, Good Manufacturing Practices. Countries around the world, including all the major manufacturers of vaccines, have adopted GMP practices. Organizations like the Food and Drug Administration are stringent in the way that they require companies to show their work, that everything at every step is controlled. We hope that we won’t have problems like that. We have mechanisms in place. Companies in North America, Europe, Japan, and Australia know how to do this. They’ve been doing it repetitively. Vaccines these days, especially those licensed in the United States or in Europe, are both safe and efficacious.
A colleague at the University of Pennsylvania makes this point that the average American parent has not seen measles. They probably haven’t seen chickenpox or mumps because of the vaccine. They consent to give their children these vaccines because they are assured that the vaccines are safe and efficacious. That is the thing that we hold as vaccine developers to a high standard. People trust us that these vaccines are going to work and that they’re not going to harm people. When you think about a COVID vaccine and you think about cutting corners, rushing, or approvals that haven’t met all of the FDA rules and regulations, it makes you worry that maybe we’re slipping in terms of that commitment to safety and efficacy.
The Head of the FDA, Dr. Hahn, published a paper in the Journal of the American Medical Association that says, “We will not stint on safety.” It’s the basis for their credibility. The reputation that the US FDA has worldwide is a highly stringent national regulatory authority. If it’s something that the FDA says is true, that it’s going to be safe and effective, they don’t want to lose that. They’re nervous when people talk about, “We’re going to expedite this. We’re going to issue the approval at a certain date.” Until we see the data and we know that it’s safe and effective, I don’t think they’ll want to do it.
It’s interesting because before I sold Cipro, we had a drug called Omniflox that they had approved by the FDA, which was similar to Cipro. It looked great but when it got on the market, we saw some issues. They had to take it off. You don’t know what you’re going to see. I’m thinking about the FDA and the WHO. I remember the drugs that we would sell. Maybe a dose would be something here in the US but would become something different in different countries. When you do a vaccine like this, is it the same throughout the world? Is it different like it is with pharmaceuticals where it can vary from country to country?
It depends on the company. Typically, a company that makes a vaccine is going to make one form. The reason is that vaccines are biologicals. They’re also given to healthy people to keep them healthy. The standard for establishing safety and efficacy is slightly different. A phase three trial with a vaccine is not a few hundred people or 1,000 people. It’s at least 3,000. That’s both the WHO and FDA minimum standard but it can involve tens of thousands of people. The COVID trials are between 20,000 and 40,000. There have been larger trials. Our HIV vaccine trial was not a true phase three, but a 2b trial, with 16,000 people. That helps you to establish a broad baseline for side effects in a normal population. Typically, anything over 3,000 gives you a good read on rare side effects.
There is one thing that we can’t predict. This is where continued follow-up and careful attention to safety is important for vaccines. We’re pretty sure that we vaccinate people in a phase three trial. Thousands to tens of thousands of people are followed for a year or two, and a vaccine appears safe. What we don’t know is maybe 3, 4, or 5 years as the immune responses, the defensive response against the vaccine begins to decrease. Are we going to see something bad happen? That actually happened with one of the Sanofi vaccines, a vaccine against the viral disease called dengue. It turns out that it looks great in year 1 and 2. After year two, we started to see maybe as a suggestion that there might be a worse disease in people who had never been exposed to dengue before. As a result, the company intensified its effort to understand that question. They answered it definitively that in fact, there was a problem. They had to change the recommendations. This is a vaccine that was in thousands of people in order to try to evaluate the fact that it was safe and effective. It wasn’t until much later that side effects appeared. They commit to initial safety and efficacy, and they also have to commit to the longer term.
That Sanofi vaccine was in development for years. COVID vaccines will be in development for a year. The companies and the organization’s countries are going to need to commit to continuing to follow-up on those volunteers. Volunteers in vaccine trials are, in a sense, brave. They’re taking a vaccine that no one knows the safety or efficacy for. They’re consenting to be vaccinated with an experimental vaccine. We owe it to them to be able to say, “Thank you for what you’re doing. We’re going to do everything we can to make sure that nothing bad happens to you.” By and large, they do. That’s an important commitment.
I realized that everybody’s trying hard to get the right answer. I look at some of the backgrounds in my family. My father was born blind from my grandmother having the Spanish Flu when she was pregnant with him. I look at the flu as a separate thing because that happened to my father. My grandfather, when he was in his 80s, took a flu shot and almost died from the reaction to it. A year later, for some reason, he did it again, and then he ended up dying and having bad reactions to the flu shot. I’m not a huge fan of taking flu shots for that reason because we don’t react well. When you said the dengue thing, I’m thinking, “Is it better to get the flu than to take a flu shot? Is it better to get COVID than to take the risk of what you could get when they go, ‘Wait a minute, look at what we found.’”
This gets to how we evaluate safety and how you appreciate the risk. Often, in the US, there’s a nearly universal recommendation for the use of the flu vaccine. In the same way, we have a nearly universal recommendation for the use of masks. In this sense, you’re not only protecting yourself against infection. I remember when I was a medical resident and I had the flu for the first time. I have never felt sicker. It is horrible. You’re febrile and you’re vomiting. You cannot feel worse. With the flu shot, we have data on millions of people who have gotten it. People have sore arms and maybe feel a little bit fatigued. Infrequently do people develop a fever.
There are specific conditions though. The flu vaccine is made in eggs and a person has an egg allergy, you have to be careful about those things. Typically, when you go to the doctor’s office or to your CVS to get it, they go through the list of things to be sure you don’t have the following. We actually now have flu vaccines that are not made in eggs, which is an advantage for several reasons. We also have now live attenuated vaccines, which your grandfather couldn’t have gotten because they’re usually given to people who are younger. There are different options now. There are even flu vaccines that can be made in insect cells. We’re getting better at it.
The other part is that flu vaccines don’t work well in the elderly. They’re the group that needs it the most. When people who are older get the flu, they have bad outcomes. Improving the responses, either giving a larger dose or mixing the flu vaccine with something that makes it more potent, is important. It’s hard to argue with individual cases of people who have bad reactions to vaccines. In general, what you’re looking at is populations of people. Not all vaccines are the same. It’s the safest thing to say. Certain vaccines have different profiles and side effects. I got the anthrax vaccine because I was in the military. I can tell you, it hurts worse with every single vaccination.
In your arm, you mean?
In your arm, it gets worse with every subsequent vaccination. That’s a recognized phenomenon so you warn people about it. When we have these kinds of databases, we can and should inform people what the expected side effects are. It’s always the best practice. When you go to your doctor or if you go somewhere and you’re and you’re having something done, you want the doctor, nurse, or the person giving the injection to explain to you what you may be feeling.
When you’re getting a flu shot, it’s working from what they learned from last year’s strain and whatever has gone by. Doesn’t it mutate? How well does this year’s vaccine work compared to last year’s?
Flu vaccines are picked about nine months before. Sometimes less than nine months. Usually, there’s a good match, but not always. I don’t know 2020’s comparison to the circulating strains. I should but I’ve been focused on COVID.
I want to get some information on COVID but I had one more question on the vaccine thing because it’s such a huge topic. You read about so much. Everybody’s saying it leads to autism, your kids are going to get this, or you’re going to get that. What is your position on all that? Are we hearing the correct information about vaccines? Who do you believe?
The autism connection was withdrawn from the journal, The Lancet. It is not true. They’ve done lots of detailed exams on people who don’t have conflicts of interest. There is no connection. Vaccines do have side effects. It’s important that we can assure people that by and large vaccines are safe and effective. As I said, over 80% of American parents give their kids may be up to 26 or 27 injections for diseases that they’ve never seen. Those injections, the CDC has calculated over a twenty-year period. It saved hundreds of thousands of lives, millions of hospitalizations, and trillions of dollars. When you look at developing countries, the benefit is even greater. For every $1 you spend on vaccines, you save $16 in health care costs. There’s a huge societal benefit. This is based on experience in developing countries.
Children who are vaccinated are more likely to finish school. They have fewer issues with developmental delays, and they have better weight. Families are less likely to go into poverty because when a child is sick, a parent has to stay home. That means that the parent is not earning income. There are all these other benefits to vaccination. In the United States, those benefits are monetary. Kids don’t die of rotavirus diarrhea. They get hospitalized. There are costs of keeping your child in a hospital when they have a vaccine-preventable case of diarrhea. I’m pretty strongly in favor of vaccination. I think that childhood vaccines, in particular, are, in general, well-tolerated. Most American parents give them and as a result, American children aren’t dying in childbirth or at young ages. If you look back in the 1960s and look at the number of cases and the number of deaths from simple things like measles, you’re astounded. It drives home the enormous benefit that vaccines have brought to modern society.
Is there a sense that they’re giving more and more vaccines that maybe some of them aren’t required? Are we giving them too early? How do you feel about that?Volunteers in vaccine trials are, in a sense, very great. They're taking a vaccine that no one knows the safety or efficacy for. Click To Tweet
We give vaccines for the diseases. All these vaccines go through a process. The company provides data that the vaccine works. The FDA licenses it. There’s an expert committee that reviews these vaccines and tries to decide whether or not to use them. You may get a recommendation as you do for the meningitis B vaccine. They don’t issue a blanket recommendation, but they say, “It works under certain circumstances. If your child is going to college and you’re worried, maybe you should consider having them vaccinated.” There are other times when they issue definitive recommendations, “You should use the following vaccine.” They do a good job of trying to make sure that they’re both protecting the American population or the American children.
How does this fit into the schedule? When you think about the burden of people who are concerned that we’re giving people too many shots, we, as human beings are exposed to thousands of pathogens. For instance, in the early stages of HIV infection, you may have 100,000, to 1,000,000 particles of the virus and every cc of blood. When you think about what you’re getting in a vaccine, that amount is minuscule. It’s because we know exactly what to put into the vaccine. We can give you what you need and you’ll develop a protective immune response against Hepatitis B because it’s the exact right thing that we need in order to develop that response. It’s a simple protein. We inject it and it protects. It’s not the whole virus.
The different vaccines are different. When you think about COVID, you’re looking at lots of different types of vaccines. Some of them are confusing, some of them haven’t ever been shown to be effective in humans. These are the RNA and DNA vaccines. Because of the horrible toll of this pandemic on more than 200,000 Americans, millions of people around the world, there’s a real pressure to get this done correctly but quickly.
I want to talk about that because there’s so much information shared about, “We’re getting a vaccine soon,” “It should be by the end of the year. No, it’s going to be next year,” “Who’s going to get it?” and, “Who’s going to manufacture it?” They’re doing all these trials all at the same time. They’re putting their money on all the different things to make sure that one of them comes out to be the winner instead of doing one at a time in sequence. What do you see, timewise, of what’s coming out? Who’s making it? What can we expect?
This isn’t that different from the situation with drug companies. Several drug companies could have different types of quinolone antibiotics like Ciprofloxacin. Different companies are testing different things. You’ll come up with slightly different indications but in the end, you have two new antibiotics in the market. The vaccine companies are doing the same thing. You’re exactly right. What the US government said is, “We don’t know which of these is going to work so we will put $10.3 billion into making sure that we have enough of the different classes to be sure that at the end of the day, there will be a vaccine that is shown to be safe and effective.”
When that vaccine is shown to be safe and effective, we don’t want to have to wait six months for it to be manufactured. What they’re doing is making some educated guesses. They’re saying, “RNA vaccine by Moderna, Pfizer, a chimpanzee adenovirus vaccine that’s the Oxford AstraZeneca vaccine, Ad26 vaccine that Johnson set up.” He’s working on protein. They’ve broken the field down into different types of vaccines. They’re saying, “By probably November to December, we may have an interim look at some of the data.” At that interim look, if there are enough endpoints and if the vaccine is protective enough, we might actually see an effect. We might see that this vaccine offers a certain level of protection. We will have a significant amount of data and information on a good portion of 30,000 people that say there are no serious side effects that are occurring in the first 3 to 5 months of vaccination. That is when you know, the vast majority of bad side effects occur. There will be a lot of information but it won’t be complete information. When faced with incomplete information but have potentially good results, the FDA may say, “We’re not going to approve this. We’re not going to give you market authorization but we will give you emergency use approval on the basis of these preliminary data on safety and efficacy.”
Which one’s showing the most promise?
That’s a tough question because we don’t know what protects. So far, all of the vaccines that are currently in phase three that have non-human primate studies and have the vaccines being tested in the United States, in Europe, all of them do. All of them protect monkeys against infection. You give the vaccine, you wait 4 to 6 weeks, or in one case, 12 weeks, you challenge with COVID-19, and the monkey is protected. How that will translate to humans, we don’t know. It’s hopeful information that vaccines may protect.
The other way you can look at is to break the vaccines down into vaccines with the best response and vaccines with responses that are our medium-range and then vaccines with a lower range. Look at a particular protein vaccine from a company called Novavax, which is based in Maryland. They generate high levels of infection-fighting proteins, we call them antibodies, that bind to and inactivate viruses. We call it neutralizing antibodies. They have the highest level of neutralizing antibodies. Novavax, you may not have heard of because they’re not quite as advanced as some of the others. You’re looking at a broad range of others, the vaccine from AstraZeneca or Johnson & Johnson, that are in a middle range of production of this infection-fighting protein. Is one better than the other? We don’t know.
The Johnson & Johnson vaccine may be effective after a single dose, which would be a good thing because the others are two-dose vaccines. The RNA vaccine from the Moderna vaccine is in that same group. It’s in the middle range of things. Look at the levels of this infection-fighting protein and you look at where the vaccine companies are, individually. AstraZeneca started in May 2020. The Pfizer and Moderna trials in the US started on the 27th of July. Johnson & Johnson started later in 2020. Of those vaccine companies, you can tell who’s in the lead because they’ve vaccinated most people but their trial was paused by the company. This is AstraZeneca. There’s suspicion that Pfizer will have data soon. There are probably similar data from Moderna though. The CEO said, “Our vaccine probably won’t be available in quantity until the middle of 2021.”
There are lots of things that could factor in. The first thing is to prove that the vaccine works. We might have that answer by the end of 2020, maybe early 2021. One of the vaccines works, it doesn’t work, and it’s safe. The next question, probably even more important questions for people who want to be vaccinated is, when are we going to have enough vaccines to be able to vaccinate good parts of the American population? Although some of the companies are ramping up production, it’s probably going to be mid-2021 before enough vaccines are available for there to be widespread availability of vaccines in the US, assuming that we can prove that one works.
The next question is, “We have vaccines, how are we going to get it?” Are we going to ship it out to doctors, offices, hospitals, and CVS or Walgreens? Are we going to have a much more structured program? Are we going to line people up at work? Are we going to do it like we did the polio vaccine? Are we going to have vaccinations in schools? All of these questions are what the CDC asked the states to get ready for and to think about as they “prepare” for future COVID-19 vaccinations. The one complication here is unlike childhood vaccinations where you take your kid to the pediatrician or to the hospital for vaccination, with COVID-19, we’re vaccinating adults and the elderly. That’s not something we do commonly. Maybe for the flu vaccine but not everyone takes the flu vaccine. We’re going to have to work on being able to deliver vaccines to adults.
Like the flu vaccine, does this mutate at all? Is it something that we have to have a new one every year? Is this going to be the panacea cure-all for all time? How does that work?
That is a great question. We have a vaccine like the rotavirus vaccine. It’s been the same vaccine since 2007 and it’s still effective in America. Rotavirus doesn’t mutate much. The question that you’re asking is how much does COVID-19 mutate compared to flu? We do have an answer to that. A good way to think of it is this. If you were to take a pin and poke it through an index card, you’d see a little tiny hole. Think of that as the amount of sequence variation in the 70,000 or so COVID-19 viruses that we’ve sequenced fully. Think about the flu. That amount of sequence variation in flu over the course of a year is about the width of the tip of your fingers, maybe 8 to 10 times more sequence variation in flu. If you think about HIV, in a single year in a single country like the Democratic Republic of Congo, it’s the size of the palm of your hand. COVID-19 doesn’t mutate much. It only takes one bad mutation. So far, we don’t think that any of them are significant that the current set of vaccines don’t cover them. We don’t have a lot of data. We certainly don’t have proof in humans that that’s the case. We’ve known about this virus for a short while. We know an incredible amount but you’d not be surprised at the amount that we still don’t know.
Everybody shows Bill Gates’ talk about how we should expect all this and you mentioned the Gates Foundation paying for certain things. How much preparation has there been for this world event in terms of looking at what could be the next virus? How surprising was it what it turned out to be?
Coronavirus has been an object of a particular amount of research because they jump from animals to humans. People call the Coronavirus promiscuous, but not in the same way we think of promiscuous but in the sense that they can use more than one host. When you think about the original SARS outbreak in 2002, that jumped from bats something called civets which are cat-like mammals, and then from civets to humans. Think about the Middle East Respiratory Syndrome, which is another Betacoronavirus in the same branch of the family as SARS. MERS started in that, jump to camels and from camels to humans.
When you think about this Coronavirus, the SARS-CoV-2 or COVID-19 Coronavirus. It started in bats, went through some we think maybe intermediate hosts, at one point we thought they were spiny anteaters or pangolins. Now, we’re not sure exactly what but it made the jump into humans. Coronaviruses are known to do this. A different group of Coronaviruses is associated with mild cases of seasonal colds. Those are the ones that are circulating all over the world. We’ve known about Coronaviruses. Influenza has a cycle in birds and other mammals like pigs and then humans.
There are groups of particular viruses that do make the jump. HIV started in monkeys or chimpanzees and jumped over to humans multiple times over the course of a century before it became the outbreak that we know now. There have been some attempts in the previous years to put together large programs to look at the kinds of common zoonotic viruses and viruses that exist in animals that can make the jump. People are now developing and they’re still at an early stage, algorithms to identify what the biggest threats are. One of those large projects was canceled before this outbreak. Research funding is research funding, so not everything continues forever, but that might have been a bit short-sighted, in retrospect. Maybe in the future, we will keep a better eye on these other viruses that readily make a transition from animals to humans, knowing that they could be a future cause of potential infection. In fact, Dr. Fauci was the author of a review with another scientist on some of the viruses that are capable of making the leap into humans. That’s something that we need to take better care of monitoring in the future. The same way we do for influenza viruses, because what will COVID-22 be like?
What if it goes on to pets? Dogs, cats, horses, whatever. Has that happened? What happens?
You mean, if it leaves humans and goes back to animals?Flu vaccines don't work well in the elderly. When people who are older get the flu, they have bad outcomes. Click To Tweet
Yeah. It starts with good dogs. You know how you get it through bats and all that, so if dogs become part of the process, then what happens?
It would depend. In the Middle East, camels because they’re common animals. People are attached to camels and are close to them. It’s potentially possible with lots of different viruses and depending on how the virus mutations affect their ability to jump from, say, bats or other animals to humans. We don’t know. It’s difficult to know.
That would be challenging with how people are attached to their animals and that happened. It’s interesting to look at much of this. I know a lot of people are doing a lot of testing. Since my husband’s a physician, they do a lot of testing before he does surgeries on people. I’ve known a lot of people to take tests, and few people come back, who I’ve known, have come back as positive. How accurate are they? I’ve seen some of them are saliva tests. Some of them are nasal tests. Which ones are most effective? Are they telling us the truth as far as are we positive or if we’ve had it at all? How accurate are they?
There are a lot of tests out there. It depends on the company and what tests they’re using. A lot of the tests, particularly early on, were approved through emergency use authorization, so they weren’t formally tested as well as they would normally be. Depending on the test and on the condition, maybe you want to have this RT-PCR test, which is the gold standard for diagnosing current active infection. They’re developing a new series of rapid diagnostic, they call them antigen tests or antigen-antibody tests, and some of them are looking much better. They’re not as sensitive but they’re sensitive enough to detect active infection. They’re useful and their turnaround time is five minutes. You don’t necessarily have to have a hospital lab in order to get the result back. That could be a real advance. They’re starting to publish data on that and they’re looking good. The thing that we don’t know yet and this is where it gets into a little bit of the specifics here. The RT-PCR test is positive for extended periods of time, and probably is positive, even after a person is not infectious anymore.
The problem with the antigen and antibody test is sometimes it takes a while. When you become infected with a virus, it takes the body a little while to generate the antibodies, the infection-fighting proteins. That could be 5 to 14 days, and depending on the level of that antibody, it may be difficult to detect it at the early stages and much more likely to be picked up at 2 or 3 weeks. In the initial stages, in the earliest part, some of that antibody will be sticking to the virus and circulating in the body so it could be falsely negative. One of the things that they need to do is not only test negative plasma and positive plasma, but they’re going to look at people who are in the course of infection to understand when it is more likely that these new tests are going to be positive. We’ll get more data at some point, but the newer tests are looking much more sensitive and specific than the first set of rapid testing that came out.
If you have had it, your antibodies show up. Can you get it again?
Yeah, good question. That’s one of the first questions you ask when you’re thinking about a vaccine. In a classic vaccine pathogen combination, say polio or hepatitis A, your normal immune response attacks the virus, eventually controls it and eliminates it. That same immune response protects you against reinfection so you have immunity to reinfection. That’s a great thing. The ability of the body to do that, under the conditions of natural infection, makes it more likely that we’ll be able to develop a vaccine against that pathogen.
With HIV, you can see how this works in reverse. The human body is never able to get rid of the virus. Your immune system can’t get rid of HIV. It’s been difficult to develop an HIV vaccine. There are cases emerging of documented reinfection and reinfection with slightly different strains. Whether or not it’s a common phenomenon or not is not known, although the strong belief is that there’s a certain amount of protection and we don’t know how long it lasts.
There was some data early on that when people get COVID-19 infection the level of infection-fighting proteins or antibodies in the blood is not particularly high. There was data that came out later that said maybe if you have these killer cells or certain types of cell-based immune responses against the virus. Even though you couldn’t measure antibodies that these T cells would protect, you would remember the virus, you would attack it and kill it. Not only that but maybe some of the T cells that were specific for the common cold type Coronaviruses would also provide some level of protection. We don’t know that that’s been hypothesized, it would be an interesting thing if it were true. We’re still waiting for more definitive proof that that’s the case.
How would you do that? One of the ways to do it would potentially be to do a challenge study. Take people who are our COVID negatives, and if they consent and they understand the risks of doing this and have no risk factor. They would be young, make sure that they would be healthy, and that we could artificially infect them, and then see if they could be reinfected. We could also vaccinate them and then challenge them. That’s something that we do. We’ve done challenge studies for malaria, cholera, and typhoid.
There’s an editorial in the New England Journal that said, “We should start thinking about a challenge model for COVID-19 because it would accelerate what we know and would make us feel more comfortable about whether people are protected and for how long? What do you have to have in the blood that protects you? You have to have massive quantities of neutralizing antibodies or will just having detectable antibodies be enough?” These are important questions and people may make policy decisions based on this information. It would be something that we could look into and there are over 10,000 people who have already volunteered to be in this challenge studies. We don’t even have a challenge to the going, but people are already saying, “Sign me up. Let me know.” We’ve done it for other diseases so it’s not like this would be the first time. The reason to do it is pressing, which is we need to understand what protects people. If there’s a way to accelerate vaccine development, that also would be a good thing.
Is there a difference in blood? Does blood type have anything to do with how people respond to any of this? We know younger people don’t get it as bad as older people and all that type of thing. What do you think are the biggest differences in how people respond to the infection? Is it mostly age?
There are two forms of the immune system, the one that we’ve been talking about, we call the adaptive immune system, it’s highly specific to the pathogen. One of the amazing things about the evolution of the human defensive or immune system is that we’ve got this immune system that eventually develops responses that are highly specific to the virus infection. If you were exposed to the measles virus, you would develop antibodies against measles. Those antibodies would not protect you against mumps or rotavirus, but they do protect you against measles. If you were to encounter measles again, those antibodies would protect you against measles in the future. We call that the adaptive immune response.
There’s a different immune response, it’s more primitive. It functions to activate the body and warn it that there’s something going on. We call that the innate immune response. The innate immune responses in younger kids or the elderly could be different. That shapes the adaptive immune response. People talk about the dysregulation of the immune response, being responsible for some of the negative consequences but I think at this point, we still are guessing. There have been some papers on why children do better. Their initial immune responses to the virus may make them less prone to have severe consequences compared to adults.
There’s more research to be done. This is all fascinating. There are many questions everybody has, but you touched on many of the things that I think a lot of people are asking. It’s great to have you on the show talking about this because it’s such an important and scary topic that a lot of people don’t know you know the answer. I enjoyed our conversation in that respect because we were able to shed some light on some of these important questions. Is there a site or something you’d like to share for people who want to know more or to follow you?
The IVI website usually posts all the interviews with the staff at IVI, not only myself but other people who are doing vaccine development as it relates to COVID or the work that a guy is doing on COVID. They’ve done a lot of interviews so there are different areas and topics. We did a blog post for NBC. A number of colleagues from around the world. You can Google those as well. The IVI website should contain a list of recent media posts. If people have questions that come through you, they can ask.
I would be happy to forward those along and the impressive history of your work, having an MD from Yale and everything that you’ve done is fascinating. Thank you, Dr. Kim, for being on the show. I enjoyed our conversation.
Thank you, Dr. Hamilton. It was a pleasure to speak to you. Such an insightful question.
I’d like to thank Dr. Kim for being my guest. We get many great guests and this was a fascinating and timely show. I hope you take some time to check out Dr. Kim’s work and check out some of the past episodes if you’ve missed any. If you’re looking for the show. You can find it on all the podcast stations and our AM/FM stations. You can also go to my website at DrDianeHamilton.com and find out more. I hope you take some time to do that. I hope you enjoyed this episode and I hope you join us for the next episode of Take The Lead Radio.
- International Vaccine Institute
- Rich Lofgren – Past episode
- Walter Reed Army Institute of Research
- Gates Foundation
- World Health Organization
- Paper – by Dr. Hahn in the Journal of the American Medical Association
- The Lancet
- Johnson & Johnson
About Dr. Jerome Kim
The Director General of IVI serves both as the Chief Executive and “Head of Mission” of this non-profit International Organization / vaccine development institute. The responsibilities include development and execution of the IVI Strategy and Mission — the discovery, development and delivery of safe, effective and affordable vaccines for Global Health. Responsibiltiies also include an important component of advocacy, fund-raising/development, and international affairs. The DG also serves as an ex officio member of Board of Trustees.
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