How Various Vaccines Work--Simplified

I was asked recently about whether the new vaccines could cause some unexpected trouble because they "modify our DNA", as opposed to previous vaccines.  To "modify our DNA" certain *sounds* kind of risky, I agree.  There was also some concern about these vaccines being able to damage the reproductive system and cause infertility.

The short answer is that this isn't a concern, but as I gave the answer, I realized there might be some important misconceptions behind this concern that could be cleared up by a longer answer.  So I'm going to give a very simplified (and therefore necessarily incorrect) explanation of some basic biology and how it relates to viruses and vaccines.

I'm going to follow this up immediately with an evaluation of the inherent risks of some of these different vaccine types and address the infertility question.

DNA, mRNA, and Proteins

DNA

Everyone knows that DNA is in some way the "master plan" for the whole body: it's the set of instructions that makes each person unique.  And I think it is a partial understanding of this that makes people very nervous when they hear about something that messes with their DNA.  I think they imagine their DNA as some single master plan that controls their entire body, and therefore anything that messes with their DNA has the potential to mess up literally anything about their body.

But there is no single "master" copy of DNA--that's not how it works.  Your DNA is replicated billions of time in cells all throughout your body.  There is nothing that can change your DNA throughout your whole body; it only exists one cell at a time and if you want to change it you have to change it one cell at a time.

Furthermore, aside from the very beginning of life when you exist as a very small set of cells, there's never actually just one version of your DNA.  DNA mutations happen all the time at the time of cell replication.  A mutation is usually just an error in cell replication--an incorrect copy.  And since these happen all the time, it's certain that you have many slightly different versions of your DNA in different cells all throughout your body.

The cellular replication process does have several error correction procedures it goes through.  For serious problems, badly messed up DNA or malformed cells are destroyed.  *Slightly* modified DNA can get through this all the time though.  Cancer exists in the grey area of this process, being mutated sufficiently enough to cause problems but *not* enough to be attacked and disposed of by the body's natural mutation clean-up system.

The bottom line is, something altering your DNA isn't the equivalent of mutating you into a different creature.  It's something that happens on the level of individual cells and the impact depends on how successfully the new cells replicate and how successful the body's immune system is at disposing of these mutations.

DNA, mRNA, and the production of proteins

Let's do a quick review on how the microscopic structures of the body are built from DNA.

Imagine DNA as a large book written in Braille.  It contains instructions for all the different things that the body builds at a microscopic level: the proteins.  It sits in the center of the cell.  When a new structure needs to be built, a piece of Play-Doh comes along and presses against the paragraph that has the instructions for this structure.  It then goes over to the cellular protein factory, which reads the impression and creates the protein by a reverse impression process.  This bit of "Play-Doh" is the "messenger RNA" or "mRNA", so called because it takes the production order "message" from the DNA to the protein factory.

How viruses hijack this process

Viruses survive by invading and hijacking this process.  To be successful, a virus needs to do the following:

1. Spread: survive outside the body for a bit of time
2. Penetrate: get into the body and survive there among the cells but not in them for a while
3. Infiltrate: gain access to the inside of reproducing cells
4. Replicate: Use the cell's own replication ability to replicate themselves, using one of various strategies:
1. Some viruses have their own DNA replication abilities; they just need to get into the protein factory in order to hijack the facilities to duplicate themselves using their own DNA.
2. Some viruses modify the DNA in the cell.  They stick their own instructions into the DNA "book" in a place where the cell will read with the mRNA.  The mRNA then takes the virus instructions to the protein factory and the factory produces more virus instead of the normal things it would instead.  NOTE: in this case, the modified DNA is not replicated.  It's just been modified so that the *virus* will be replicated.
3. Some viruses just produce their own mRNA and arrange so that their mRNA gets sent to the protein factory instead of the normal mRNA.  The end effect is basically exactly the same as modifying the original DNA; it just skips a step.
5. After replication, each copy starts over again at step 2.

How the immune system defeats viruses

This is really complicated, but to overly-simplify (and skip a bunch of steps), the body determines that there is a foreign invader and starts working on developing new proteins that are custom-shaped to latch on to the foreign particles and somehow neutralize them ("neutralizing antibodies").

In the case of Covid (and other coronaviruses, actually), it seems that the primary thing that the body's immune system attacks is called the "spike protein".  This is the spiky protrusion around the outside of the virus, and it is used by the virus for step 3 ("Infiltrate")--it works kind of like a skeleton key to break into the cell.  The neutralizing antibodies that the body produces bind to the spike protein, so that it no longer fits into the key hole.  The virus particles are thus not able to enter cells and not able to reproduce.

How vaccines also cause the immune system to produce neutralizing antibodies

The goal of a vaccine is to trigger the same immune response that the real virus does, but without the virus actually replicating throughout the body, causing the disease.  There are several strategies that have worked for this:

1. Infect the person with a disease that is really similar to the original disease, but much less severe.  The smallpox vaccine was like this; cowpox is a disease that works much like smallpox, so that the antibodies that the immune system produces to counteract it happen to also work against smallpox.
2. Take a virus and somehow neuter it so that its ability to replicate is destroyed.  I believe the MMR vaccines work in this way; I think they use UV radiation to damage the virus.  Then they inject you with a quantity of the virus.  The virus particles retain the protein structures necessary to invade cells (I think) and the immune system generates neutralizing antibodies to those structures.  There is a risk in this method that the culture is not completely neutralized and enough viable virus is left to replicate and cause the disease you are trying to vaccinate against.  (It's a low risk; about 1 in 1 million).
3. There are new kinds of vaccines that try to be much more targeted in how they operate.  Rather than using a full virus (either a weak relation or a weakened form) for the body's immune system to react to, these vaccines get cells to produce just small parts of a virus.  There are two main new technologies being employed to do this, which I will now describe.

The newer vaccines

Adenovirus vector vaccines

Adenovirus vector vaccines are essentially genetically modified cold viruses.  They still operate like normal viruses up until they invade your cells.  After this, when it comes time for them to inject their genetic replication DNA into the cell, this genetic replication code has been replaced with a specified set of instruction instead.  So the messages that get sent to the protein factory aren't "build another copy of this virus", but rather just "built this specific structure" instead.  In the case of a coronavirus vaccine, the specific protein that they cause to be produced is the spike protein.  The infected cell therefore generates that spike protein, which the body's immune system recognizes as foreign material.  The immune system therefore generates antibodies to the spike protein of a virus without ever having had exposure to the whole virus.

Since an adenovirus vaccine does not have replicating code, it will not replicate throughout the body.  The modified virus will infiltrate those cells with which it comes into contact at the site of the injection, those cells will operate differently for a time, and those cells will then be destroyed and disposed of by the body's immune and waste disposal systems.

mRNA vaccines

mRNA vaccines aim for the same effect as the adenovirus vector vaccines, but with an even simpler delivery method.  With these vaccines, we just straight up manufacture the messenger RNA fragments that will tell the protein factory to produce the spike protein.  Our chemical gene manufacturing processes have gotten good enough where we can mass produce small segments of RNA--so that's what we do.  We then encapsulate bundles of these mRNA fragments into lipid nanoparticles so that they can survive for a while inside the body.  ("Lipid nanoparticles" sounds exotic, but it is less so than you might think.  It's actually not dissimilar to the process of making mayonnaise, it's just a much finer emulsion.) When these are injected into someone, a lot of them bump into cells and get absorbed into them.  The mRNA fragments then get into the cell protein factory, causing those cells to start producing some spike proteins, thus triggering the immune response.

As with the adenovirus vector vaccines, there is no replication code injected, so the vaccine can only cause a set number of cells to produce spike proteins.  Again, these cells will be disposed of by normal waste disposal processes.