Vaccines have long been considered settled science and the backbone of preventive care from infancy to adulthood in the United States and around the world. Backed by funding from the National Institutes of Health, physician scientists like Arturo Casadevall have dedicated their careers to this lifesaving field.
Casadevall, who holds a PhD in physical chemistry and has been working on vaccines for 30 years, describes vaccines as "humanity's greatest invention."
But increasingly vaccines once thought of as routine care are the target of skepticism in the face of unproven safety concerns and weakening rules that no longer make vaccines a requirement, says Casadevall, chair of the Department of Molecular Microbiology and Immunology at the Johns Hopkins Bloomberg School of Public Health. This hesitancy has led to a decline in vaccination rates among kindergartners in the U.S. As medical exemptions from school vaccination requirements rise, the country is experiencing outbreaks of deadly diseases like measles, which public health officials had once considered to be eradicated thanks to widespread vaccinations.
Casadevall spoke about vaccines with Public Health On Call podcast host and fellow public health researcher Joshua Sharfstein, director of the Bloomberg American Health Initiative and vice dean for Public Health Practice and Community Engagement at the Bloomberg School. Their conversation covered the basics of vaccines—how they work, the science behind safety, the systems built to ensure children are immunized against life-threatening diseases, and more.
"I have gotten at least eight shots, and I think that they are a remarkable invention and they are responsible for saving millions of lives," Casadevall says.
What follows is an edited excerpt of Sharfstein's interview with Casadevall. Listen to the full episode here as part of Public Health On Call's new Vaccines 101 series.
How would you describe a vaccine?
It's been known since antiquity that when individuals got an infectious disease and recovered, they were immune for the rest of their lives and that observation meant that the body could learn from the experience to then protect itself against future encounters with the same microbe. So what vaccines do is they teach the body to protect itself against a specific microbe without taking the risk of an infection. The net result is the immune system reacts to it and you're protected as if you had actually gotten sick in the first place.
Let's say we had a extremely tiny camera and we were following the injection of the vaccine into the body. What would happen at the cellular level?
The vaccine is in the liquid that the doctor gives you and it goes through small channels into these small organs that we have called lymph nodes. They're part of the immune system and, right there, the immune system is able to break down the vaccine and to learn from its components. So the way to think about it is that the shot is a set of instructions to make both antibody and submediated immunity such that if you ever run into the microbe, you can defend against it.
So what is in a shot? Can you explain the different kinds of vaccines?
We have dozens of vaccines and they are very different. You can take a microbe, kill it, and give it as a vaccine. You can take a microbe or a virus and attenuate it and then it no longer causes disease. It's lost virulence, but the body sees it and deals with it and learns from it just as if it was the wild virus. And you can take a piece of a bacteria or a virus and then prepare it in a way to become a vaccine. The vaccines generally have the instructions, which is what we call the antigen, to make an immune response. And then they have other things like stabilizers, things to make sure that bacteria don't grow on it. They tend to be relatively simple formulations. Sometimes they have what are known as adjuvants, which is almost like giving a booster to increase the body's response to the vaccine.
How do the mRNA vaccines work?
Very differently. With mRNA vaccines, what happens is a virus is composed of protein and it's composed of what we call nucleic acids. Instead of going into the lymph nodes, it goes into the muscle and then when it goes into the muscles, they make the protein of the virus, and then the immune system recognizes it and then basically provides an immune response. And that's why your arm is often sore because the proteins are being made locally and the immune system is responding to it.
There are some viruses, notably HIV, where people have been trying to make a vaccine for decades. Why is it that there are some conditions, disorders, or pathogens that can be fought with a vaccine, but for others it's been so hard?
Image caption: Arturo Casadevall
If a virus has the capacity to change very rapidly, the immune system cannot keep up with the changes. And that's what happens with HIV. You simply can't keep up. But I would say that progress continues to be made, and I'm confident that eventually one will find a vulnerability that can be targeted by the immune system and that then one day we could have a vaccine to eradicate HIV.
Another very difficult virus to make a vaccine for was respiratory syncytial virus or RSV—that was discovered, by the way, in our department in the 1960s. They tried to make a vaccine that was a killed-virus vaccine, and they just did not elicit a protective immune response. In fact, people often got sicker than they would have otherwise. But then came molecular biology and structural biology, and people were able to solve what was the key to how the cell would see a virus. And they were able to make a new vaccine that was licensed last year. It's a phenomenal vaccine, and it's a testament to human ingenuity.
Could you talk about how you think about stimulating the right kind of immune response versus an immune response that maybe doesn't really matter that much for protection?
So let's take COVID-19. When you get an infection with COVID, you mount an antibody response and a cell media response to all the pieces of the virus. But the only one that matters for protection is going to be the spike protein, which is this protein that sticks out. You don't need all the other proteins to make a vaccine. So yes, not all viral proteins are of equal importance and scientists work very hard to try to identify the key protein that elicits protective immunity. And once you have that, that's often the first step to making a successful vaccine.
Are there any vaccine misconceptions you would like to correct?
I think that it's not surprising that the general population may not have a full understanding of how vaccines work. But the one thing I would say is that the vaccines that are available are incredibly safe. They're all being tested. They don't cause autism. They save lives. I will give you one anecdote from when I trained as an infectious disease doctor. We used to cover pediatrics, and I was covering Jacobi Hospital and Montefiore Hospital in the Bronx—every week we would have a baby or a young child with hemophilus type B. One third of those children died, one third of those children had developmental problems as a result of having a meningitis, and one third recovered without any problems. A vaccine was introduced in the early 1990s, and I never saw another case again.
Conjugate vaccines are another miracle of modern medicine. We have them against pneumococcus and we have them against meningococcus—the cause of meningitis in young adults. These are life-threatening diseases of high consequence, even if you survive. So the vaccines to protect us against them truly are modern miracles.
