How the Covid Vaccines Actually Work

As it would look on a "Magic School Bus" Field Trip

This is an extremely simplified explanation (translation really) of the academic language and technical concepts behind the mRNA platform. As such, there is necessarily a small degree of technical imprecision that is unavoidable.

The reason I am writing this is primarily to give over to people a sense of the intricate complexity of the covid vaccines, which stands in stark contrast to the doctors and experts - especially the local doctors whom the average person looks to for guidance and reassurance about the vaccines - all of whom constantly claim that the vaccines are just like traditional vaccines that have been around for decades.

Hopefully, readers can come away with an appreciation for the novelty and complexity of the covid vaccines, and how we are quite literally flying blind so to speak regarding what sort of biological effects these vaccines have or will have in people. At minimum, readers can take this with them to their local doctor to show the doctor, or at least themselves, that the doctor has no functional grasp of these vaccines and how they work whatsoever.

Also, I was told that the Magic School Bus TV Series is available on Netflix, although I cannot personally confirm this to be the case, but I would enthusiastically recommend it for kids based on my own childhood experience (if they are going to be watching TV regardless).

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Conceptually, vaccination is the introduction of a dead or attenuated non-pathogenic substitute (whether in full or in part) into the body that possesses the identical salient features, or epitopes, used by the immune system to identify and neutralize the substituted-for pathogen. In other words, it is showing the immune system a ‘model’ of what the real virus looks like so it figures out how to deal with it in advance. The basic idea behind this is that you can get the benefits of viral exposure without the risks or harms of viral infection - you get to have your cake and eat it too.

Prior to covid, all FDA-approved publicly deployed vaccines simply intruded the substitute pathogen itself into the body, where it was identified and catalogued by the immune system resulting in firm immunological memory to various molecular regions of its proteins, or epitopes.

What the Covid Vaccines Did Differently than Prior Vaccines

The currently approved crop of covid vaccines, however, employ an undeniably brilliant revolutionary design, whereby instead of injecting the actual pathogen or piece of the pathogen, these vaccines instead infiltrate genetic material, either messenger RNA (mRNA) or a type of DNA that will create mRNA once it is within the cell. This genetic material is encased within a protective sheath – a lipid nanoparticle in the case of the mRNA vaccines, and a ‘deactivated’ routine adenovirus cell for the DNA vector vaccines (J&J/AstraZeneca). This ‘protective packaging’ also serves as the delivery vehicle that ‘guides’ the mRNA into a cell (and also serves as an adjuvant to evoke immunological response mechanisms to make the immune response stronger and more potent).

Once infiltrated into a human cell, the mRNA strands temporarily hijack a portion of the cell’s protein-making machinery to manufacture a specific group of proteins – in this case, the parts of the famous Spike (S) protein - targeted by the vaccines’ developers.

(The mRNA strands are ‘souped-up’, ‘refined’ to improve the molecular stability and success rate of the % of mRNA’s turned into spike proteins; in other words, reducing the percentage of ‘duds’. It is further capped on both ends by specialized molecules that protect/’guide’ the mRNA and make it ‘easier’ for the cellular machinery to ‘read’ or ‘use’ an mRNA strand.)

The cell then manufactures spike proteins until the artificial mRNA strands are ‘used up’. (There is a type of synthetic mRNA developed that has the capacity to ‘self-replicate’, which would mean that the yield from each individual strand of mRNA could be hundreds or thousands of discrete proteins, which is admittedly quite cool. The current vaccines do seem to have employed this fancy type mRNA judging by the runaway spike production that seems to be happening in some people, to simplify a very complex topic somewhat inaccurately.)

Some of the newly minted spike proteins eventually migrate (overly simplified) to the surface of the cell, becoming visible and identified by constantly circulating immune cells. The immune system’s identification of this aberrant spike protein presenting on the surfaces of what should be healthy cells activates a broad immunological response to the now-identified antigenic protein, which through enough interactions becomes “primed” to marshal quickly and aggressively against any pathogen presenting these antigenic epitopes, should one subsequently invade the body. This is a simplified description of the “action sequence” executed by the vaccine after injection.

Spike Protein Design Modifications

Turning now to a more granular analysis, the spike protein encoded for in the mRNA (hereon used to refer to both the mRNA and DNA vaccines) was engineered with a few modifications. A conventional SARS-CoV-2 spike protein has two basic components, referred to as S1 and S2. The S1 is a sort of mushroom-ish shaped ‘head’ perched atop the S2 ‘stem’.

The spike protein’s primary function for the covid virion, as is well known by now, is to ‘break into’ a human cell and infiltrate the covid virion’s RNA past the cell membrane, where once inside the cell can ultimately hijack the cellular protein synthesis/reproductive capabilities, forcing the cell to manufacture thousands of new covid virions. (What the cell is really producing is actually just very long protein strands - a chain of amino acids - that have to be clipped at the right places so they can fold into their respective shapes properly, after which the finished proteins are assembled into a new covid virion.)

The function of the S1 subunit is to bind to a surface protein present on many types of human cells called an ACE2 Receptor. Once bound, a different cellular surface protein, TMPRSS2, cleaves the S1 from the spike protein, leaving a ‘decapitated’ S2 subunit.

The S2 Subunit of the Spike Protein

Now, the S2 is comprised of a series of proteins, the majority of which are bound together linearly, like a series of links in a chain. The end of the S2 - where it was connected to the S1 - is capped by a Fusion Protein (or peptide, abbreviated FP), whose function is to fuse with the cell membrane. This fusion starts a chain reaction of sorts that eventually results in fusion of the virion membrane to the cell membrane, creating a ‘door’ into the cell which the virion’s RNA can ‘swim’ through.

What is important to note, however, is that the physical shape and structure of the S2 components substantially reconfigures with the S1’s decapitation to a realignment that activates the Fusion Protein (one scientist described this as similar to opening a pocketknife, where the knife is the S2 subunit, and the blade is the FP). This is referred to as the S2 prefusion and postfusion states. One critical distinction between the pre- and post- fusion states is that the presenting protein characteristics of the S2 are registered as distinct epitopes by the immune system, such that exposing the immune system to S2 proteins in a post-fusion state would not induce immunological memory to the S2 epitopes of the prefusion state, which is how the Spike protein presents on a free-floating covid virion. Think of how a folded pocketknife looks and feels versus an unfolded one - that is sort of how the immune system is only going to ‘remember’ the spike protein version that is presented to it (the immune system doesn’t ‘understand’ that they are the same thing.)

A longstanding technical obstacle to designing anything around the Spike Protein, however, was that the prefusion state of the S2 subunit turned out to be unstable in unattached Spike Proteins (even without being chopped up).

So several mostly routine modifications to the spike protein were therefore introduced at critical junctures where the chemical bonds between the different S2 components undergo alterations in order for the component proteins to physically realign. This was accomplished through strategic replacements of specific amino acids in the protein segments where the intermolecular chemical bonds are changed to execute the S2 realignment. The primary modifications were replacing amino acids Lysine and Valine (#’s 986 & 987 if I remember correctly) - the juncture connecting the CH (central helix) and HR1 (heptad-repeat [domain] 1) segments - with Proline (a significantly more “inflexible” amino acid), to lock them in their prefusion alignment. (They also added a “Trimerization Tag” to the base of the S2 (where the HR2 protein segment attaches to the comparatively ‘obese’ body of the S2).)

Another modification made was the addition of an ‘anchor’ protein segment to anchor the spike proteins to the cell membrane, tethering them to the cell that created them & preventing them from floating away and possibly into circulation (well, in theory anyway).

The S1 Subunit of the Spike Protein

Similar to the S2, the S1 subunit also has multiple conformations likewise the subject of tactical design considerations. A significant mutation cooked up – this one definitely qualifies as a mutation by virtue of its distinctly mutant-like quality – was to rig the S1 subunit so that there would be 3 exposed receptor binding domains (RBD’s) (imagine the 3-headed dog from the 1st Harry Potter book). The reason for this choice was that antibodies to a piece the RBD were comparatively superior to antibodies targeted to other spike protein epitopes. The RBD is the ‘sticky’ or ‘business’ end of the spike protein, the part that actually attaches to the ACE2 to start the whole binding process to break into the cell. This meant that the RBD was an ideal candidate for vaccine targeting, for these two reasons:

1. antibodies bind more tightly or firmly to the RBD

2. neutralizing the RBD would neutralize the spike protein on a covid virion

Unfortunately, to quote one study, “the use of RBD in vaccines is compromised by its limited immunogenicity owing to its small molecular size and possible mixed forms of multiple complexes” (ie, it’s hard to get this to work).

The solution settled upon was to engineer the S1 to be locked in a somewhat unnatural and ‘stuck open’ ‘activated’ position. (Alas, a side-effect of this would be enhanced binding affinity from the sticky ends being locked into an ‘armed’ position (as opposed to the ‘closed’ conformation where the RBD is nestled underneath the other segments of the S1)). Critically, the S1’s capacity to bind with ACE2 receptors seems to have been left intact at minimum, and has certainly never been proven to be eliminated, which vaccine manufacturers carry burden of proof to establish.

J&J added a further modification to the Furin Cleavage Site - that’s where the TMPRSS2 protein slices off the S1 and also one of the strongest indications that SARS-CoV-2 is a lab creation - to essentially remove it, so the TMPRSS2 protein wouldn’t break the chemical bonds between the S1 and S2 and flip the S2 attached to the cell membrane into its “open”/”activated” position.

It is true that an effect of these modifications is to sharply reduce the possibility of the S2 to fuse with a cell membrane even if it would get loose into circulation - if the S2 can’t ‘unfold’, then the Fusion Protein can’t fuse with the cell membrane. This seems to have been [mis]understood by some ‘experts’ as neutering the Spike protein of any pathogenicity, that is to say, a capacity to (harmfully) disrupt normal biological functions within the body, which is definitely not the case.

Other modifications (that are also be a potential source of safety concerns) include commonly utilized routine enhancements such as ‘codon optimization’. A very simplified explanation is most amino acids are coded for in multiple nucleotide sequences; and using the preferential choice of the host cell results in higher efficiency and quality manufacturing the protein. Unsurprisingly, the vaccine designers went all in on the codon optimizing, choosing to encode for maximum protein translation at maximum speed with maximum efficiency. There are some serious concerns with the effects of this max output design - what they did is somewhat akin to running a machine on the maximum level for an extended period of time - what usually follows is the machine starts to get unusually hot while making unusual noises and shaking violently. Basic rule of thumb: going for the absolute max is rarely a good idea.

Basically, the spike protein encoded for in the vaccine mRNA was supposed to be a sort of inverse Frankenstein non-monster.