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  • Writer's pictureRyan Allen

A primer on vaccines

Vaccines have undoubtedly been a hot topic in recent years, and when the weather starts to get colder, related discussions always seem to resurface. Before I share any information or thoughts on vaccines, I want to first emphasize that this post is not universally applicable to all vaccines. Every vaccine is different—not only across different diseases for which you are vaccinating, but also between types of vaccines for the same disease (i.e. mRNA vs. live attenuated virus vs. recombinant protein, etc.). Not to mention, guidelines are always shifting in the world of vaccines and infectious diseases because they are such dynamic processes. As came to light during the heights of the COVID-19 pandemic, infections do not stop to allow us time to research and determine the best course of action. Rather, things happen on the fly, and virtually all recommendations are subject to change. Here, I will try to provide a basic introduction to vaccines through established information across pretty much all forms of vaccines, and through a lens that is largely time-independent and unlikely to change anytime soon.

Starting with the basics, it can often seem mysterious to the public how exactly vaccines work, and what is in them. This is understandable, because it is a little complicated to understand without any sort of background in immunology. For the most part, I think of there as being three components of any vaccine: the antigen, the adjuvant, and the delivery vehicle.

The antigen is the part of the vaccine that is specific for the disease against which the person is being immunized. The goal of any vaccine is for our immune system to build up a response against this specific antigen, such that when the real disease comes around, we have a defense already built up, ready to fight it off. The antigen is often given in a small enough quantity to avoid getting sick from the vaccine itself, but a large enough quantity to initiate a proper, memory-producing immune response. Antigens are typically fragments of proteins because that is what our immune system reacts to, although the antigen in a vaccine is not always a protein. Many are, but take the example of mRNA vaccines. These give the body a dose of mRNA, the molecular code for proteins, so our cells can read the code and produce the protein themselves. As it turns out, in certain cases this allows for the protein to be more efficiently detected by our immune system and generate a response, which is why this form of vaccine has emerged as a popular method of presenting antigen these days. (While on the topic of mRNA vaccines, it is worth addressing the concern of this genetic code sticking around in our bodies, which is not the case. Unlike DNA, mRNA is a very transient, less stable, and rapidly degraded form of nucleic acid code, and therefore there is no need to worry about it persisting in our cells long-term after administration.)

Next up in our three components is something called the adjuvant. You can almost think of this like the ignition to get the engine going and start the immune response. (Now this may be where things start to get a little technical, but the complexity of immunology is such that even this is really simplified; I will do my best to just highlight key points as we go.) In a natural encounter with a pathogen (which is any disease-producing thing, such as a virus, bacterium, fungus, etc.), we will first have the activation of our innate immune system, which is less specific for the exact pathogen, but quick to respond when it just notices anything foreign to the body. This innate response triggers a whole cascade of inflammatory processes, and the release of various factors that aid in generating an adaptive immune response (the long-term memory that we want). The main takeaway is that we pretty much need this base of innate response/inflammation in order to solidify the reaction we want to the vaccine, which is to generate memory. Recall that the antigen is the desired subject of the adaptive, memory response; we want our bodies to generate a reaction against that, and remember it. Adjuvant, therefore, is the stimulator of the innate response. It often contains characteristic molecular patterns of things like bacteria, which we know our bodies will easily react to, in order to broadly trigger our immune system. We are innately wired to respond to these things, and once we get our immune system up and running, we are optimally prepared to react to the antigen.

Lastly, the critical components of the vaccine usually must be packaged in something called a delivery vehicle. Luckily, our body has a lot of defense systems built up that prevent things from the outside world just making their way into our cells. So, usually when we administer anything into the body, it will quickly be eradicated before it gets anywhere near our target tissue unless we package it into something stable inside the body. Nowadays, these usually involve fat-soluble molecules that can form a bubble around the active vaccine ingredients, which are water-soluble and do not mix with fat (think oil and water). Because of their solubility, the delivery vehicle can more easily cross cell membranes, which are also made up of fat-soluble components called lipids. Thus, the vehicle carries the real important, active components into the cell. A popular delivery vehicle these days consists of lipid nanoparticles, which have shown to be very effective in producing cellular uptake of their contents. To my knowledge, this is really all these particles do once inside the body, and they are relatively stable and inert. All sorts of lipids are present in our bodies, and with this vehicle literally designed for stability, it is clearly not something concerningly foreign to us, or that we can’t clear with relative ease.

While there is certainly much more to say on this subject (and this post will require a part 2), I hope this provides some understanding of the mechanism behind vaccination, and eliminates some of that mystery behind those shots you are regularly encouraged to get.


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