Vaccines 101: The Basics of Vaccines and Vaccination
How do these silent heroes of public health actually work?
Vaccines are the silent heroes of public health. Not only do they help protect people everyday from disease—they’ve helped to eradicate deadly pathogens like smallpox. Over the last 50 years, vaccines have saved the lives of an estimated 154 million people, according to the WHO. Over a hundred million of those lives were infants. But how do they actually work?
In this Q&A, adapted from the January 27 episode of Public Health On Call, Joshua Sharfstein, MD, vice dean for Public Health Practice and Community Engagement, and Arturo Casadevall, MD, PhD, MS, an infectious disease physician and chair of the Department of Molecular Microbiology and Immunology, discuss the basics of vaccines: their biology, how they work, and new developments in vaccine science. This is the first of a series of podcasts from Public Health On Call about vaccine basics from the molecular level to global policy.
How would you describe a vaccine?
Vaccines are humanity's greatest invention. 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 protect itself against future encounters with the same microbe. Vaccines teach the body to protect itself against specific microbes without taking the risk of an infection.
How does that actually work within the body? How does the immune system address vaccines?
The immune system has a wonderful layered system of defenses, and when it comes to vaccines, two major defenses are activated. One of them is antibodies, which are proteins in the blood. Then you have something called cell-mediated immunity, which are cells, usually T lymphocytes.
You almost always get both. From a regulatory point of view, you often measure antibodies in people and basically know how effective a vaccine is in a population.
What happens at the cellular level when you get a vaccine?
When you get a shot, the vaccine is in the liquid. It goes through small channels into organs called lymph nodes, where the immune system breaks down the vaccine and learns from the components. The way to think about it is: The shot is a set of instructions to make both antibodies and cell-mediated immunity, so if your immune system ever encounters the microbe, it can defend against it.
What is in that shot?
We have dozens of vaccines, and they are very different. Some are made with killed viruses. Some use an attenuated microbe or virus that can no longer cause disease. It's lost virulence, but the body sees it and learns from it just as it would the wild, or naturally occurring, virus. Other vaccines use just a piece of a bacterium or a virus.
Vaccines generally contain “instructions,” which is what we call the antigens—whether the killed or weakened pathogen or piece of it—to evoke an immune response. They also contain other things like stabilizers, which ensure that bacteria don't grow in them. Some contain adjuvants, which increase the response to the vaccine. Vaccines tend to be relatively simple formulations.
How do mRNA vaccines work? Are they different?
A virus is composed of protein and nucleic acids, like DNA and RNA. mRNA vaccines contain not the virus or a piece of it, but just the instructions—the mRNA—for making part of the virus. Again, that goes into the shoulder, but instead of going to the lymph nodes like viruses or pieces of them do, mRNA goes into cells in the muscle. Those cells essentially read the instructions and make the protein of the virus. The immune system then mounts an immune response to that protein, which it will remember if it ever encounters that virus.
That's why your arm may be sore after an mRNA vaccination: because the proteins are being made locally, and the immune system is responding to it.
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?
Not all viral proteins are of equal importance, and scientists work very hard to try to identify what the key protein is that elicits protective immunity. Identifying that is often the first step toward making a successful vaccine.
Let's take COVID as an example. When you get a COVID infection, you mount an antibody response and a cell-mediated response to all the pieces of the virus. But the only piece that matters for protection is the spike protein, because that protein is essential for the virus to replicate in the body. The mRNA COVID vaccines only produce the spike protein.
There are some viruses, notably HIV, that people have been trying to make a vaccine against for decades. Why can some pathogens be fought with a vaccine while others can’t?
If the virus has the capacity to change very rapidly, the immune system cannot keep up with the changes. That's what happens with HIV.
Imagine the immune system is a cop, and you say, “Go after the person with the red coat!” By the time they get there, that person has changed their coat to green, and then to blue, and then to brown. You simply can't keep up.
But progress continues to be made, and I'm confident that eventually someone will find a vulnerability in this system that the immune system can target, and that then one day, we could have a vaccine to eradicate this terrible virus.
Another very difficult virus to make a vaccine for, was respiratory syncytial virus (RSV). RSV was discovered in our department in 1957. In the 1960s they tried to make a killed virus vaccine, and it did not elicit a protective immune response. In fact, people often got sicker than they would have if they had not received it. But then came molecular biology and structural biology, and people were able to find 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 a testament to human ingenuity.
What are some common misperceptions about the biology of vaccines?
There are a lot of misconceptions. 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 have all been tested. They don't cause autism. They save lives.
When I trained as an infectious disease doctor, I used to cover pediatrics at Jacobi Hospital and Montefiore Hospital in the Bronx, and every week we would have a baby or a young child infected with Haemophilus influenzae type B bacteria. One-third of those children died, one-third had developmental problems as a result of having meningitis, and one-third recovered without any problems. A vaccine was introduced in the early ’90s, and I never saw another case again.
Conjugate vaccines—a type of inactivated bacterial vaccine—are another miracle of modern medicine. We have them against pneumococcus and also meningococcus, the cause of meningitis in young adults. These are life-threatening diseases of high consequence, even if you survive. And you don’t see them in vaccinated individuals.
This interview was edited for length and clarity by Morgan Coulson, an editorial associate in the Office of External Affairs at the Johns Hopkins Bloomberg School of Public Health.
