Thread by @Dr_TJRicks

The early SARS remix vaccines are mRNA vaccines.

These are pretty different from the normal vaccines that are used and mRNA vaccines are becoming the hot new kid on the block.

Let's break down this review and learn the pros and cons of this technique.

nature.com/articles/nrd.2…

alright so first let's distinguish between normal vaccines and mRNA vaccines.

Conventional vaccines come in 5 types:

Live, Attenuated Vaccines
Inactivated vaccines
Toxoid Vaccines
Subunit Vaccines
Conjugate Vaccines

Let's go through each quickly

Live, attenuated vaccines have a weakened version of the bacteria or virus that you're trying to gain immunity from.

Basically, it's a boxing match where the bug has one armed tied behind its back and your immune system should be prime Mike Tyson.

Easy Win. No rematch

Inactivated vaccines completely kill the germ during vaccine production.

These vaccines often need multiple doses to keep up immunity. This is due to the germs not actively doing anything inside your body, so your body only recognizes it as something foreign, but not active

Then you have toxoid vaccines that use weakened versions of the toxins that certain bacteria make that can cause illness. So your body learns to fight the toxins that the bug produces.

Subunit vaccines only include pieces of the bug, not the whole active bug.

Then you have the last vaccine type called a conjugate vaccine.

Some bacteria make these complex sugar coatings called polysaccharides. Bacteria that form biofilms use these sugar chains along with proteins and DNA to form a kind of molecular cloak to hide from our immune system

Conjugate vaccines take these sugar chains and stick bait at the end that will trigger an immune response.

Now your body can not only detect the biofilm, it can also detect the antigens (immune triggers) that the bugs make so you can squash em out

So where do mRNA vaccines fit into this? Guddd Kwestion

If I were to classify this vaccine type, I would call it a subunit vaccine because the mRNA uses your native biomachinery to make viral pieces that your body reacts to, not the whole bug.

How does it do this?

Let's chat about mRNA right quick so you can understand what it does

mRNA stands for Messenger RiboNucleic Acid

Hopefully, the Ribonucleic Acid part rings a bell since RNA is closely related to DNA, DeoxyriboNucleic Acid.

mRNA is the gap between DNA and protein synthesis

In order for your body to make the proteins that are encoded by your DNA, your body goes through a two-step process called transcription and translation.

First, your mRNA plays telephone with your DNA and picks up a protein code. This is called transcription.

During transcription, your body uses a protein called RNA polymerase to form pre-mRNA

*Pro-tip
Anything that ends in the suffix -ase generally means it's an enzyme, a type of protein that makes chemical reactions happen easier by using a couple different factors.

Let's break the word down.

Polymer-ase

So we have an enzyme that creates polymers. A polymer is a large molecule made by regularly repeating parts called monomers.

The monomers in this case are the nucleoside bases below.

DNA and RNA are biological polymers

So

RNA polymerase II uses the DNA template to make pre-mRNA during transcription.

it gets refined further to mature mRNA which is then sent to ribosomes that read the mRNA to make proteins. this step is called Translation, as the mRNA is translated into a protein.

Aight let's stop here and refresh

If we are using an mRNA vaccine, the vaccine bypasses the first step of protein synthesis, transcription.

The mRNA is primed with the protein code so it can go straight to translation of the viral piece.

This is why I say its a subunit vaccine

Ok so now that you have the loose background on how mRNA works, let's get into the pros and cons of mRNA vaccination.

Let's start with the pros

1) Safety: since these vaccines don't actually use the bug you're trying to gain immunity from, you can't get infected by it.

mRNA can be chopped up by your regular cellular processes and you can even change the timing of the mRNA chop shop by making small chemical modifications to the mRNA template.

More changes can also down-modulate other side effects that may happen.

2) Better delivery methods: in the early days of mRNA research, one of the huge hurdles that has gotten much smaller is getting the mRNA where it's supposed to go. Recent advances have done 2 things.

*Stabilized the mRNA piece to resist degradation
*Increased translation rate

Recent advances show formulation with different carrier molecules such as:

*Lipid nanoparticles
*Polymers
*Proteins
*Protamine-mRNA complexes

In all of these, mRNA is still the minimum genetic vector, so you don't have to worry about being immune to the thing carrying the mRNA.

3) Can be scaled to the moon efficiently: This is more of a profit/captialistic pro moreso than a health pro

These mRNA pieces can be constructed very quickly and scaled very efficiently based on the high yields of in Vitro transcription reactions

So those are some of the pros. Let's talk about the cons now.

1) Storage: Most mRNA vaccine products that are used for study are stored frozen at -70 celsius

You obviously can't give someone a cold shot like that so room temp or fridge stable formulations are needed.

One of the leading platforms, RNActive, was reported to be active after stringent water removal called lyophilization (\ lī-​ˌä-​fə-​lə-​ˈzā-​shən \) & storage between 5-25 degrees C for 3 years & 40 degrees C for 6 months. These conditions need to be maintained during transport

2) No Official Regulatory Guidance: As of right now, there is
*no official RNA specific regulatory guidance*
from either the FDA or the EMA, the European Medicines Agency

Meaning that there are no stringent, RNA specific guidelines for

*Manufacture
*Quality
*Safety
*Efficacy

In a lot of ways, mRNA vaccine production is still the wild west because the guidelines that are currently in place are guidelines used for other vaccines

mRNA vaccines currently fall into the broad category of genetic immunogens like DNA plasmids and gene therapy vectors

3) Safety: mRNA vaccines have side effects.

Here are a few:

*Severe injection site reactions
*Potent type one Interferon Inflammatory responses that can lead to autoimmune disorders (@dualchemy)
*Oedema (Fluid based swelling)
*Possible thrombosis caused by increased clotting

Keep in mind that these are short term

*There are no long term studies of all possible mRNA vaccine side effects.*

Naked mRNA vaccines turn these up but they are possible with all delivery methods.

So what type of mRNA vaccines are the SARS Remix vaccine?

Let's take a look

These vaccines to my knowledge are nucleoside modified mRNA (modRNA), mRNA where nucleosides have been replaced by naturally modified nucleosides or synthetic nucleoside analogs to produce a specific protein

In this case, it's the spike glycoprotein that embeds into your cells

Once the mRNA template is read, the spike GP expresses itself on the outside of your cells, which theoretically should produce an immune response from your body, specifically in the form of antibodies for that protein sequence.

So here's the thing about mRNA vaccination and vaccination in general.

It doesn't work well if your immune system is ass.

The reason why these vaccines require multiple doses is that mRNA is degraded very quickly, meaning your body may not produce immunity in time.

If it doesn't, you need to get a *booster* shot, which is essentially what the second dose is.

Again though, if your immune system is already either fighting off another active infection or is weakened, it will be harder for your body to make the necessary antibodies.

Either way it goes,

you still have to go through your immune system.

Your immune system is and has always been the key. Doesn't matter if you get the vaccine and your immune system is trash because you'll need multiple doses to make your immune system fight back

mRNA vaccines are very cool on their face and just repurpose your native protein synthesis process to make proteins that aren't in your genetic code

However, again no long term side effect data, and it *still* needs a good enough immune system to work well.

Vaccine or not,

Strengthen your immune system
Strengthen your immune system
Strengthen your immune system

*Fin*

https://twitter.com/Dr_TJRicks/status/1341926525499809797?s=20