“It’s just like riding a bike!”
We usually say this when we’re trying out a task or a skill that we may have learned long ago, and have not used for a while, but can still execute like no time has passed. Think back for a moment to that time when you were learning this persistent skill. What exactly did you need to learn that stuck with you all this time? Your brain and muscles learned how to stay balanced, how to pedal and how to steer, and how to do all of those things at once. It was a pretty complicated task to learn.
But all that learning probably took place in steps. Maybe you started out on a tricycle, so you could learn how to pedal and steer without the added complication of balancing on two wheels. Maybe once you moved to a bicycle, your parents added training wheels, so you could continue practicing pedaling and steering while adding learning to balance without the risk of toppling over a thousand times and getting injured or discouraged. Training wheels, in fact, gave you the opportunity to teach your brain everything it needed to know, so when you finally took the training wheels off, you could rely on the memories you formed to fully develop your ability to ride your bike successfully.
Vaccines do to your immune system what training wheels did for your balance when you were learning how to ride a bike. Like how training wheels teach you how to steer and pedal without allowing you to fall and hurt yourself, a vaccine teaches your immune system how to fight an infection without you the risk of getting sick for a long time or sustaining some type of permanent damage. How do we build a vaccine that achieves that delicate balance, where it can teach the immune system to fight an infection without exposing it to a debilitating disease?
To understand this, let’s explore how the immune system can be taught anything. Your immune system is composed of two different parts, the innate immune system and the adaptive immune system, which function differently, both in time and role, but work together to fight off infections. So what happens when you get an infection?
How Your Immune System Fights Back
Your innate immune system is the first responder of your immune system. It recognizes general signs of infection, such as when there’s foreign genetic material or bacterial molecules inside your cells. Importantly, the innate immune system generally functions the same in every person, meaning that each person will recognize the same molecules. The innate immune system doesn’t distinguish one kind of infection from another, except in general ways (such as telling the difference between a bacterial infection versus a viral infection, for example), but it still plays an incredibly important role: it leads to the activation of the adaptive immune system, which ultimately kills off the infection.
Your adaptive immune system is where the real business of fighting an infection happens, even though it responds more slowly than your innate immune system. Your adaptive immune is composed of the ultimate infection-fighting team of B cells and T cells. B cells are responsible for surveying the body for signs of infection outside of our own cells, while T cells look for signs of infection that originate within our cells.
Both cell types need to express a very eclectic mix of receptors to identify the vast diversity of infections that are out there. But with our simple, relatively static genome, matching the diversity of bacteria and viruses that are out there can be a challenge. There are over a thousand different pathogens that can attack our body at any given moment, and our adaptive immune system has to be ready to recognize any of them. But it’s such a waste for our genome to house over a thousand genes that encode B and T cell receptors. But our cells have figured out a way to generate such a random collection of receptors without housing a gene for each individual one.
Our cells start with a much smaller set of genes and randomly reconfigure each one in multiple ways to generate different receptors. By randomly stitching together multiple gene segments in each individual cell to encode a single receptor per cell, each T or B cell expresses a different, unique receptor. This process could potentially generate an estimated one quadrillion to 100 quintillion T cell receptors and one quintillion to one hundred quintillion B cells receptors. That is roughly equivalent to the number of grains of sand on Earth! In practical terms, though, our bodies produce far, far fewer T and B cell receptor types, but they still produce more than enough for our immune systems to recognize a diverse array of antigens.
Notably, the process of stitching together these genes to encode the receptors for T and B cells happens while you’re developing, meaning that you do not inherit the T and B cell receptor sequences from either of your parents and your set of T and B cell receptors will be different from every other person on the planet. Even identical twins don’t have the exact same set of receptors.
It instead comes down to what infections you encounter during your lifetime: The first time a T or B cell comes in contact with a foreign molecule, called an antigen, that particular cell divides to produce an army of cells to fight the infection. After the infection is gone, most of those T or B cells retreat and die off, but a small group of them stay at their posts and become memory cells—cells that have been “trained” to recognize an antigen and can recognize it earlier, enabling the immune system to act much faster in response to the infection if it ever comes back.
The first time a T or B cells sees an antigen is the equivalent of a kid hesitantly and shakily riding that two-wheeler for the first time, while those memory cells are the kid who jumps on a bike and confidently flies down the street because he or she has been on a bike before and remembers how to ride it. Although this “memory” doesn’t get passed down to your children, it’ll at least help you stay healthier in the future.
This ability of your adaptive immune system to remember past infections is the key to a vaccine’s success. In fact, a lot of basic research has gone into understanding what makes the adaptive immune system work so that others can create vaccines that exploit this system’s ability to remember infections. What researchers have found is that vaccines typically require two extremely important components, an infection-specific antigen and an adjuvant, as well as other components so the vaccine can be stored and given to people safely. Here’s what all of these components are for:
1. An antigen
The first important component of a vaccine is an antigen from an infectious bacteria or virus, such as the influenza virus, that spurs your innate immune system into action. Identifying the right antigen to use, which most people respond to, though, is trickier than you might think.
Recall that to build up your adaptive immune system, your cells generate T and B cells by mixing and matching dozens of different genes. Since each of us generate a different set of receptors, not every person’s immune system will recognize the same antigens. Therefore, researchers need to find an antigen, usually a protein or a part of a protein (called a peptide), that T or B cells from most people can recognize. This can be an extremely laborious process, especially for bacterial infections, such as tetanus, because bacteria possess way more proteins that could potentially act as antigens than viruses. The process of identifying a bacterial antigen that most people can recognize might involve screening individual proteins from a bacteria or virus for their ability to activate T and B cells from a number of different people.
2. An adjuvant
Antigens, while specific enough to activate T and B cells, are inefficient at generating an adaptive immune response. This is because the innate immune system needs to be activated first to prime the adaptive immune system.
This is adaptation is meant to safeguard us against the immune system from responding to any old bacteria (such as a bacteria that is important for your gut health) or virus. But this adaptation can also be a challenge in developing an effective vaccine; it makes it harder to wake up the adaptive immune system from its slumber. Fortunately, scientists have a pretty good idea about what activates the innate immune system and they will often include something in the vaccine called an adjuvant to do just that. An adjuvant is another molecule that the innate immune system responds to and is responsible for eliciting an innate immune response that will prompt an adaptive immune response, enabling it to produce of memory cells.
3. Inactive components
Our vaccine now has all the ingredients it needs to protect you from an infection: an adjuvant to activate the innate immune system, which will prime the adaptive immune system to respond, and antigens to activate the adaptive immune response to a particular bacteria or virus and generate those all-important memory cells. What else is needed to build a vaccine? Generally, vaccines need to be kept in some sort of fluid, such as sterile water, saline, or a protein solution, so it can be stored and injected or sprayed. Additionally, to prevent the antigens in the vaccine from degrading and losing their potency, vaccines also typically include stabilizers and preservatives. These prevent degradation due to light and heat and stop microbes from growing in the solution that can make you even sicker. Sometimes, depending on how the vaccine is made, a vaccine will also contain antibiotics leftover from production of the antigens and adjuvants.
The Importance of Vaccines to Public Health
Vaccines are an important part of disease prevention in public health (read more about whether they’re truly safe and effective here). Because of vaccines, life-threatening diseases such as smallpox and polio have been virtually eliminated in the U.S. and other developed countries. Other highly contagious, potentially debilitating diseases that primarily affect infants and children, such as measles and whooping cough, have been greatly reduced in frequency and severity since the development of childhood vaccines against them.
If you have more questions about what vaccines you need to stay healthy, ask your doctor.
Cara Froyd recently received her Ph.D. in immunology from the University of Chicago.