Thread by @FLermyte

Thread:
Basic Vaccine Explainer or: How I Learned to Stop Worrying and Love the Jab

This one’s going to be a long read with a decent chance of me going off on tangents/rants, so I recommend you grab yourself a cup of coffee/tea and get comfy

I wrote most of this as a series of DMs to someone with some vax anxiety recently. Sharing now (with permission) in case it’s still useful to anyone. Thought it was all fairly well known by now, but I’ve been hearing more “gene therapy” and “not a vaccine” nonsense again lately

Your immune system is great at killing things that shouldn't be in your body, once it's learned to recognise them. This takes time, which is why it takes weeks to get over a flu. Your body needs this time to produce a targeted weapon against the virus. That weapon? Antibodies

For a cold or flu, spending one or two weeks feeling poorly is OK, but Covid can do irreparable damage. So the trick is to develop antibodies in advance. Once your body's made those, it remembers the recipe and can re-create them much faster

Think of a chef creating a new dish - lots of trial and error, but once they get it right, they can bang out dozens of orders in an evening. So what you want is a way to "train" your immune system - to let it develop its recipe - without posing a serious danger to your health

No points for guessing that that's what a vaccine does 😉

So what (some) traditional vaccines do, is take a virus or bacteria, kill or deactivate it, and introduce it into your body. That way, it doesn't infect you, but your immune system gets the required target practice

It's an art. The bug needs to be "dead" enough to not make you sick, but "threatening" enough for the immune system to mount a response. Most anti-vax memes are about the latter part (making it threatening). This is what things like alumina (known as “adjuvants”) are for

It’s also this triggering of an immune response that can cause side effects like fever, headache, muscle soreness, etc. Has nothing to do with actual infection (this is impossible, as we’ll get into) – it’s just that your body briefly has a similar reaction as to infection

Now, the key target for coronaviruses is a protein called "spike". It's important because it's the part that binds to human cells and allows infection. So obviously, you want antibodies to attack that protein - if it can't get into your cells, it can't hurt you

This is why you hear about “neutralising” antibodies. They bind to the spike and disable it. Antibodies that bind somewhere else and are non-neutralising will be much less effective at protecting you. In rare cases (most notably dengue) they can worsen disease

This is known as antibody-dependent enhancement (ADE) where non-neutralising antibody binding can make a virus more mobile within the body. As said, this is very rare, and the fact that Covid reinfections tend to result in mild or asymptomatic cases shows that it’s not an issue

Similarly, the vaccines aren’t 100% effective (true for any vaccine, against any disease) but the people who got infected post-vaccine tended to have either no symptoms or much milder illness thanks to their antibodies – they certainly didn’t have “enhanced” disease!

Large-scale real-world data on SARS-CoV-2 has therefore put the ADE idea to bed. Anyone claiming it’s a (vaccine-related) concern demonstrates poor understanding of vaccines, immunity, and a few old studies on mice involving a vax candidate against the 2003 SARS virus

Also, in dengue (where ADE does occur) it was discovered in reinfections. The vaccine won’t cause your body to produce any antibodies that it wouldn’t produce during infection. This also handily debunks the nonsense spouted by some about infertility or endothelial cells

Now a small detour about proteins, DNA, and RNA - including mRNA. Just about everything in your body gets done by molecules called proteins. Antibodies are proteins. Enzymes are proteins. Proteins are responsible for making your muscles contract. Etc. etc. etc.

Proteins are basically long chains of molecules called amino acids. Think of them as beads on a string. Humans have 20 amino acids (20 colours of beads). You can make an infinite variety of proteins by changing the string length, and the colour/order of the beads (amino acids)

These proteins get made in parts of your cells called "ribosomes" Thing is, ribosomes need to know the type and order of amino acids to string together. This is actually what DNA is for, fundamentally. The "genetic code" is nothing but a set of instructions for making proteins!

And in fact, each "gene" consists of the instructions for making a particular protein
(Full disclosure: I'm simplifying a bit here, and for example not mentioning some "tricks" to store info for more than one protein in one gene – a bit like making a ZIP file)

The ribosomes (protein factories) are in a part of the cell called the "cytoplasm", which is basically everything that's not the nucleus of the cell. And the DNA (which has the instructions for the ribosome) is in the nucleus. So how do the instructions get to the ribosome?

Well, the DNA never leaves the nucleus, and the ribosomes never enter it (it’s a separate, well-protected compartment of the cell), so there has to be some intermediary. A "messenger" if you will. Messenger RNA, to be precise 🙂

Also known as mRNA

RNA is similar to DNA, but less stable, due to some chemistry I won't get into. Just know that RNA breaks down in minutes under normal circumstances, while we've extracted DNA from millennia-old samples. Which is why it's a good thing our "blueprint" is stored in DNA

By the way, I’m going to be playing fast-and-loose with RNA vs. mRNA. The reason for the “m” is that RNA has a few other functions – in fact, ribosomes consist largely of ribosomal RNA or rRNA. Glossing over some nuance, but just assume I’m always talking about mRNA

So your cells use RNA as a temporary copy. Inside the nucleus, a gene (DNA blueprint) gets copied to RNA, which gets sent to the ribosome, which then makes the protein based on instructions in mRNA. After this, the highly unstable mRNA breaks down quickly

The thing about viruses is they’re not really alive. That's because they lack most of the machinery I just described. Coronavirus is really just some fat (“lipid envelope” if you want to sound sciencey) and protein (including spike protein) surrounding a bit of RNA

Once the spike protein docks with a human cell (specifically a receptor protein on the cell surface called ACE2) it injects its RNA. That RNA then finds a ribosome and - since the ribosome does nothing but translate RNA to protein - it starts cranking out virus protein

This has lots of effects - the coronavirus RNA has around 25 genes, so that number of proteins are produced. Broadly, this results in (1) virus RNA being copied, (2) more fat/protein shells being built, and (3) assembling protein, fat, and RNA to make more coronavirus copies

Obviously, having your cells’ machinery hijacked is bad, which is why you get sick. Now the thing is, like I said, the coronavirus RNA has about 25 genes. What do you imagine would happen if I injected your cells with just one? Specifically, let's say the gene for spike protein?

Your ribosomes would make that protein, because translating RNA to protein is all they know how to do. Your immune system would recognise it as being foreign though. And your body would mount an immune response

The beauty is, there's never any intact virus involved in the whole procedure. All but one of the genes the virus needs to reproduce are never introduced into your body! Which is why this type of vaccine is incredibly safe and also incredibly targeted

So now we come to the difference between the Pfizer, Moderna, Oxford, and J&J jab. And it's actually quite simple. See, all of those use the mRNA that encodes the spike protein, and rely on getting that RNA into your cells and ribosomes, in order to train your immune system

The Pfizer and Moderna vaccines ("mRNA vaccines") are just the mRNA in a fat droplet ("lipid nanoparticle"). Oxford and J&J actually "hollow out" a common cold virus known as an adenovirus, and put in the spike mRNA. Here's a complete list of the Pfizer vaccine ingredients:

Moderna is similar. Cholesterol and 1,2-distearoyl-sn-glycero-3-phosphocholine are very well known and aren’t at all worrying. ALC-0315 is more novel, and helps stabilise the mRNA

ALC-0159 is a surfactant. It has an end that likes to hang out in water, and an end that prefers oily molecules. This makes it perfect for stabilising oily lipid molecules (like the ones surrounding the mRNA) in water. It’s similar to how soap lets you rinse off grease

ALC-0159 is also the molecule that has a poly(ethylene glycol) (or PEG) group, which is suspected to cause allergic reactions in very rare cases. PEG is an extremely common molecule in daily life though – I see it as a contaminant when analysing samples in my lab all the time

The components with ‘phosphate’ in the name help stabilise the pH (mRNA doesn’t survive in acidic or alkaline conditions, and you wouldn’t want to inject an acid or base anyway). Sodium chloride and potassium chloride are kitchen salt and fancy sodium-free salt, respectively

The mix of the 4 components in the previous tweet is known as phosphate-buffered saline (PBS) and used in biology everywhere. Sucrose is ordinary sugar, and helps protect the nanoparticles during freezing and thawing. Finally, water is… well I hope I don’t need to explain that

So that’s a look at the mRNA vaccines. Fancy delivery platform, probably some future Nobel prizes, but none of the components are particularly worrying to a (bio)chemist. Also, they all get eliminated from your body in days/weeks

In the hollowed-out adenovirus vaccines, it "infects" your cells, acting as a tiny syringe, but instead of introducing the RNA with all the genes to make more adenovirus, it only introduces the gene for a coronavirus spike. After that, the process is identical to mRNA vaccines

In both cases, the vaccine itself (viral RNA or adenovirus) sets off enough alarm bells in your body that no adjuvant is needed, which also helps out the safety profile (even though modern adjuvants like alumina are already very safe)

For adenovirus vaccines, your body might already have antibodies against the adenovirus "shell", so the trick is to use an unusual one. This is why the Oxford vaccine uses the shell of a chimpanzee adenovirus. Any talk of "chimpanzee DNA" or "monkey cells" is complete bunk

Update since I originally wrote this: Novavax! This is more similar to “classic” vaccines in that they use virus protein with an adjuvant. The spike protein is produced artificially (similar to how insulin is made) so again, no intact, disease-causing virus is ever involved

The adjuvant is a non-traditional one, made of extract from the Q. saponins tree, formulated with cholesterol and phospholipids. Nothing in that recipe worries me as a biochemist, but I’d love to know how they came up with this! It seems very effective though!

Sources for the Novavax info, since it’s less established than the rest here:
link.springer.com/article/10.100…

nature.com/articles/s4158…

nejm.org/doi/10.1056/NE…

I want to make a point about “person X had a vax and then Y happened” anecdotes. “Y” being, “got Covid”, “died in the next month”, etc. Remember there are over 200 million “persons X” by now, and coincidences happen. Case in point, a Moderna trial subject was struck by lightning

So while it can’t be ruled out that Big Pharma is a front for Big Lightning, it’s more likely that all these so-called side effects are statistical blips, and as valid as saying “person X said that “scone” rhymes with “gone” and they got hit by a bus!”

Second-to-last point, you might hear about "modified nucleosides" when talking about mRNA vaccines. Nucleosides are the building blocks of RNA, just like amino acids are the building blocks of proteins

There's a class of HIV inhibitors with nasty side effects that’s based on modified nucleosides, but these use a completely different principle than modified RNA and are chemically totally different. Not even apples and oranges to compare the two - more like oranges and goldfish

Sometimes mRNA needs to hang around for a while, to make more copies of a protein. Your body regulates RNA longevity by chemically modifying it to make it more stable. Vaccines use this natural RNA stabilisation trick to make more spike protein to train your immune system

It’s still a matter of hours or days before the modified mRNA gets cleared though. And - since all of this happens in the cytoplasm - there's zero chance of the RNA getting into the nucleus and doing anything to your DNA (so don’t believe the “gene therapy” nonsense)

For reliable vaccine info on Twitter, check out @gorskon @Dereklowe @ENirenberg @andrew_croxford @RachelAlter007 @VirusesImmunity @florian_krammer @JamesWard73 @profshanecrotty @thereal_truther @skepticalraptor @doritmi @carlsmythe @VaxxersAnti

Many more, but – 280 char limit

Some resources to point out: Here’s an in-depth look at the ingredients of both mRNA vaccines, along with their development and supply chain
blog.jonasneubert.com/2021/01/10/exp…

Here’s an analysis of the specific RNA sequence used by BioNTech/Pfizer that goes into far more detail than I have
berthub.eu/articles/posts…

Final point: the best vaccine is the one that goes in your arm. All are safe, and very effective at preventing illness, hospitalisation, and death. They also stop/reduce transmission. If you have the chance to get one, 90% of the world envies you
#VaccinesWork #ThisIsOurShot

Thanks (and congratulations) to anyone who made it this far. Consider liking/retweeting if this was useful to you. Think I’m done ranting for a while