Let’s Talk About Vaccines
Disclosure: I wrote this article and used AI as a “professional editor” to refine and shorten overly long or complicated sentences.
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The COVID-19 pandemic dramatically accelerated the use of mRNA vaccines. Estimates of lives saved through COVID-19 vaccination — the majority of which relied on mRNA technology in countries such as the United States and much of Europe — are in the millions. At the same time, the speed at which these vaccines were developed and deployed, combined with concerns about side effects (whether scientifically supported or not), led some people to question not only mRNA technology, but vaccination more broadly. This warrants a closer look at vaccines.
Biotechnology and medicine have made remarkable progress over the past decades, as highlighted in several of my other articles. Yet despite these advances, many diseases can still only be treated supportively by managing symptoms rather than restoring health. And even when a disease can be cured, an obvious question remains:
Wouldn’t it be better not to get sick in the first place?
This is where vaccines come into play. Traditional vaccines are designed to prepare the body in advance and rely on a fundamental property of the immune system: memory. Once the immune system has encountered a threat, it remembers it. If the same threat appears again, the immune response is faster, stronger, and far more effective, often clearing the threat before we even develop symptoms.
Importantly, the idea behind vaccination is far older than modern medicine. Long before viruses, bacteria, or immune responses were understood, people noticed a crucial pattern: those who survived certain infections often did not get sick again.
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The Origins of Vaccination
In the 1700s, physicians observed that individuals who recovered from smallpox were protected for life. This led to early attempts at variolation — deliberately exposing healthy individuals to material from smallpox sores in the hope of inducing a milder infection. While variolation sometimes worked, it carried substantial risk and could still result in severe disease or death.
In 1796, Edward Jenner made a critical observation that changed everything. He noticed that milkmaids who had been infected with cowpox, a much milder disease, appeared to be protected against smallpox. By intentionally exposing individuals to cowpox rather than smallpox itself, Jenner introduced a far safer way to induce immunity. The shift from exposing people to a deadly disease to using a safer substitute laid the foundation for modern vaccination. Even the word vaccination comes from Jenner’s finding, as it derives from the Latin word vacca, meaning cow.
While Jenner originally used cowpox, later smallpox vaccines relied on the closely related vaccinia virus, which could be produced in a standardized way and used safely at scale. This refinement ultimately enabled the global eradication of smallpox, officially declared in 1980.
Since then, vaccines have dramatically reduced (or effectively eliminated) diseases such as polio, diphtheria, tetanus, measles, rubella, and many others. The elimination of a disease requires widespread herd immunity, meaning enough people must be immune so that the pathogen can no longer spread efficiently. Herd immunity does not need to be achieved worldwide to protect vulnerable people; local vaccination rates matter enormously.
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How Vaccines Continued to Evolve
A brief disclaimer: The article is intentionally simplified. The underlying science and regulatory landscape are considerably more complex, but the core concepts can be grasped without needing all of those details.
Since Jenner’s time, vaccination has become progressively safer and more precise. Many modern vaccines no longer use live pathogens at all. When live viruses are used, they are highly attenuated, meaning they are weakened to the point that they cannot cause disease in healthy individuals. Before looking at the different vaccine strategies in detail, it helps to briefly revisit the immune system — specifically, the parts that vaccines are designed to activate.
Our immune system is highly complex, but it can roughly be divided into two parts: the innate immune system and the adaptive immune system.
While vaccines are designed to establish primarily long-term protection through the adaptive immune system, they also activate the innate immune system, which is required to build a strong and durable adaptive response. Many vaccines include what are referred to as “adjuvants”. These are substances that amplify the immune response by activating the innate immune system.
The adaptive immune response is very precise and highly tailored. When a virus or bacterium enters the body, immune cells recognize specific molecular features on that pathogen. These recognizable features are called epitopes, which represent only small parts of a virus or bacterium. Once our adaptive immune system has memorized these epitopes, it can provide an effective immune response the next time the same epitopes are detected.
Vaccines generate immune memory through both antibody-producing B cells and T cells, which are part of the adaptive immune system. B cells produce antibodies, which are highly specific for their intended target, allowing for a very strong and effective immune response. T cells play two key roles: so-called “helper T cells” coordinate the immune response, which includes signaling B cells to produce antibodies. “Killer T cells” directly seek out and destroy cells that have already been infected by a virus.
Effective vaccines focus on presenting the adaptive immune system with the most “informative” epitopes — the parts of a pathogen that are most likely to trigger strong and lasting immune memory.
This can be done by using inactivated or attenuated vaccines, exposing the immune system to the whole pathogen, allowing it to recognize multiple epitopes at once. The most common example is the standard flu vaccine: Influenza virus is grown in eggs and then inactivated for use as a vaccine.
Instead of using the whole pathogen, subunit vaccines use only purified pieces of the pathogen — often the most important epitopes. A common example is the Hepatitis B vaccine, which contains only a purified surface protein from the virus rather than the whole virus. Because these vaccines do not contain live components at all, subunit vaccines are particularly well-suited for people who are immunocompromised.
Toxoid vaccines present inactivated (detoxified) toxins rather than the pathogen itself, teaching the immune system how to neutralize the harmful effects produced by the infection. These vaccines are used for diseases in which illness is caused primarily by toxins released by bacteria. Well-known examples include the tetanus and diphtheria vaccines, which protect by inducing antibodies that neutralize the toxins responsible for nerve damage and severe respiratory illness.
The latest category is “genetic vaccines”, which include mRNA vaccines and viral vector vaccines. Rather than delivering the epitope directly, these vaccines provide genetic instructions that our own cells use to produce the epitope. In viral vector vaccines, those instructions are delivered inside a harmless carrier virus (ironically, we use viruses to protect us from viruses). In mRNA vaccines, they are delivered as a strand of messenger RNA (mRNA). Both approaches trigger a particularly strong immune response because the immune system encounters the epitope in a context that closely resembles a real infection — produced from within the cell rather than introduced from outside.
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Understanding mRNA Vaccines
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Quick reminder: our genome is made up of DNA (deoxyribonucleic acid), and the information is copied into a messenger called messenger RNA (mRNA), which consists of RNA (ribonucleic acid). This messenger is used by the cell to make the final product, the protein.
This is also what happens when we have a viral infection. Viruses rely on our cells to make viral proteins. This is why mRNA vaccines work exceptionally well to protect against viral disease. Instead of injecting a virus, or a fragment of a virus made outside the body, an mRNA vaccine delivers a set of instructions that allows our own cells to produce a small and harmless piece of the virus that includes key epitopes. Importantly, the mRNA does not change our genome and is short-lived, which means it is broken down naturally over time.
Because this approach mirrors natural infection more closely than many traditional vaccines, mRNA vaccines tend to generate robust immune responses. Just like during a viral infection, the protein is produced inside the cell, closely mimicking how the immune system encounters viral proteins during real infection. This is one reason why mRNA vaccines strongly activate both B cells and T cells, resulting in effective protection.
mRNA vaccines require a delivery system to ensure that the mRNA can enter cells. Current vaccines use lipid nanoparticles, which are fat-like particles that stabilize and deliver the mRNA into cells. In addition to their delivery role, lipid nanoparticles also have an adjuvant-like function by activating the innate immune system.
mRNA vaccines are also faster to design and easier to adapt. Once the genetic sequence of a pathogen is known, new vaccines can be developed quickly by adjusting the mRNA sequence. Beyond infectious diseases, mRNA vaccines are also being actively researched for applications such as cancer vaccination (see below).
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Vaccine Side Effects, Risk, and Reality
No medical intervention is entirely risk-free, and vaccines are no exception. Most common side effects occur because vaccines intentionally activate the immune system, and include soreness at the injection site, fatigue, fever, or muscle aches. These are all signs that the immune system is responding as intended. These effects are usually mild and temporary.
More serious side effects can occur, but they are rare. Vaccine approval is based on a risk–benefit framework, meaning that a vaccine is approved only if the risk caused by vaccination is far lower than the risk posed by the disease itself.
To put this into perspective: for the measles vaccine, the risk of a severe allergic reaction is estimated at about 1 in 1,000,000 doses, while measles infection itself leads to hospitalization in roughly 1 in 5 unvaccinated cases in the U.S. and can be fatal, even in a hospital setting.
There are many “believed” side effects, that are often fueled by myths or misinformation. Most of these claims have been thoroughly investigated and scientifically disproven. Please read my “Measles Can Be Deadly — But It’s Preventable” article that covers many concerns in great detail.
Here, I want to focus on mRNA vaccines. The mRNA itself is short-lived and biologically harmless, and does not alter our genome. Current mRNA vaccines use lipid nanoparticles to deliver the mRNA and help trigger the immune signals. Lipid nanoparticles are not toxic, do not remain in the body, and do not alter our genome. Lipid nanoparticles are made of components that our body naturally produces, such as phospholipids (the same fat-based molecules that form cell membranes) or cholesterol, but they also contain synthetic parts, such as “PEGylated” lipids. While PEG (polyethylene glycol) is not a problem for the majority of people, it can cause allergic reactions in a small number of individuals.
Lipid nanoparticles are also not a new invention; they have been used to deliver drugs for decades.
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Beyond Prevention — Vaccines as Treatment
Traditionally, vaccines have been preventive, designed to stop disease before it starts. But vaccines can also be developed for diseases where the immune system struggles to recognize a threat. One prominent example is cancer.
Cancer vaccines are not designed to prevent the onset of disease, but to help the immune system recognize and attack existing tumors. These therapeutic vaccines often target tumor-specific features and are increasingly personalized, sometimes tailored to an individual patient’s cancer.
mRNA technology has accelerated this field by enabling rapid design of vaccines that encode tumor-specific epitopes. In this context, vaccines begin to resemble targeted drugs — stimulating immune responses against disease rather than preventing exposure.
While most cancer vaccines are still in clinical development, they represent a shift in how we think about vaccination: not only as prevention, but as a form of immune-guided therapy.
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Closing Thoughts
Vaccines are not new, and they are not mysterious. They are the result of centuries of observation, refinement, and biological insight — continuously improving in safety, precision, and effectiveness.
mRNA vaccines did not reinvent vaccination. They refined it.
Understanding how vaccines work — and why they work — is essential to navigating public debates with clarity rather than fear. And as vaccine technology continues to evolve, its role in medicine is likely to expand far beyond infectious disease alone.
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