SARSCoV2 Vaccines, Risks and Escape Infections:
To, look at Vaccine escapes and their potential side effects on individuals, one has to look at the virus and its interaction with the human cell. The SARSCoV2 virus latches onto the human cell, like a bee to a hive. The anchoring point is the ACE2 receptor and the binding site is called Receptor Binding Domain. The ACE2 receptors are fairly ubiquitous in the human tissues, from the nasal passages to the gastrointestinal tract to the gallbladder, the testis, the kidneys and so on.
The virus carries a S Protein, besides the “E,” or Envelope, “M,” or Membrane, and “N” or Nucleocapsid proteins which are represented in the virus as specific codons on the mRNA. The S protein presents itself on the surface of the virus as a spike, and there are plenty of them, like a nerf ball with spikes. Once the spike encounters the ACE2 receptor the spike is activated via protein Furin, it latches on like a key to a lock, and opens a pore on the surface of the cell releasing the RNA of the virus into the cell itself through the pore. Once inside the cell (endocytosed) it cytosolizes and then proceeds to create multiple copies of itself that get ejected into the blood and tissues to infect more cells for replication. The virus basically commandeers the cell machinery to create trillions of mini-me(s). And the infection proceeds on its fast gallop. The body’s immune system cells exposed to the antigen (finding this non-self S-Protein) charges its immune cells to create antibodies virus represented as the antigen (also called the epitope or presented antigen) The tug of war creates a tremendous amount of inflammatory material such as Interferon. Interleukins and other Cytokines to put an end to the virus. Victory in this fight is a full recovery with a lasting knowledge of the offending agent, the virus itself. Defeat is mostly a product of an unchallenged and progressive immune response that kills the host.
Vaccines against the SARCoV2 are made of many different shades (listed below). Two most popular and being used globally are the mRNA based. All vaccines need the mRNA sequence that codes for the Spike Protein, since that is the initiating eventful source of the infection. The differences are based on the carriers or vectors that carry the mRNA into the human cell. The current crop includes: four major vaccine kinds that are (nearly) ready: mRNA, viral vector, protein subunit and attenuated/inactivated virus. The J&J vaccine is a bit different it uses the DNA (more stable hence does not need cold storage) which then recodes the mRNA within the cell and its carrier is an attenuated non-infectious adenoviral vector that it uses to climb into the cell itself.
The RNA metaphorically speaking is like the Random-Access-Memory or RAM. It is short-lived and volatile. To permanently store such memory in the hard drive, the Computer will prompt you if you want to permanently save the information that is in the clipboard that residing in the RAM part of the computer. The Pfizer and Moderna vaccines use the volatile mRNA and use lipid—nano-proteins (LNPs) as the envelopes that contain the mRNA in its core. The outer boundary layer is composed of positively charges hydrophilic lipids. Once the vaccine is injected into the upper arm muscle, most of it is taken up by the lymph nodes in the armpit (hence the enlarged lymph nodes noted after post vaccination). There the vaccine product is endocytosed (sucked in) into the cell and releases its bounty for the Ribosome to work its magic. The Ribosome translates the codons (3 nucleotides constitute one codon) into one of the 20 Amino Acids. A Protein is a collection of Amino Acids. A collection of those proteins makes the Spike.
The trick used by the scientists and the manufacturers is to prevent the cell from recognizing the mRNA as a “self” because if it did, it would destroy the mRNA on the spot without any immunity being produced. The magic used by Pfizer, as the company states in its paper: BioNTech/Pfizer vaccine uses modified mRNA to evade the cell’s own immune system “There are also the modified bases like pseudouridine/1-methylpseudouridine that get read off at the ribosome like their native cousins but make the mRNA strand both more stable and less likely to set off an immune response against itself.” Both the Moderna and BioNTech/Pfizer vaccines use such modified mRNA. These mRNA vaccines work very well, and this is likely because they not only generate S proteins, they do so in a very specific way, thus programming our immune system - it mimics the virus itself. For the J&J the selling point being that it is a DNA product hence very stable, compared to RNA which is a fragile entity. Thus, the viral vector vaccines using DNA, as in J&J vaccine, do not need special deep freezing or other restrictions. Contrary to the ongoing but uncharted debates of whether the mRNA will insert itself into the human DNA, the data is fairly conclusive that it does not.
The Spike protein has a function to perform and it must have the same predilection for the ACE2 receptor to bind to the RBD site with equal vigor and “a firm spine”. If the Spike is lax in any way, the merger does not take place. The brilliant scientists have taken on the task of making the spike protein more rigid by using a slightly modified S gene where two amino acids have been changed into Prolines, adding a lot of stability. In lab testing, this increased expression by a factor of fifty. A more rigid version was proposed to keep the spikes active and fruitful in their messaging. Without such strengthening of the Spike protein the function of the spike collapses and renders the vaccine impotent.
What about the Risks from the mRNA vaccines, you might ask? A valid question that needs to be addressed. There are several Adverse Events noted on the CDC VAERS reporting site. These adverse events occurred in “causal proximity” of the vaccine delivery to the individuals. Several thousand deaths have also been reported. Theoretical arguments have been proposed as reasons for such events. Regarding the short-term adverse events such as the Bell’s Palsy there is an argument that the LNPs carrying the mRNA may be engulfed by the nerve tissue and create an anti-inflammatory response leading to the nerve dysfunction. Additional data to support such a claim comes from experimental mice models where the mRNA was noted in the lymph nodes, liver and even in the brain cells (neurons). The last site must give one pause because if true it might suggest the possibility of a longer-term effect manifesting as a Autoimmune inflammatory response causing a chronic brain disorder such as ALS or Multiple Sclerosis. Of note here is that this is a theoretical argument and thus far from and without merit, yet still worthy of thought and future safety. Long term chronic effects take time to develop and thus far no factual data exists. However autoimmune nature of side effects have been well-documented as Immune Thrombocytopenia due to the clumping platelets via platelet factor activation (PF4) which can both cause blood clots as well as relative thrombocytopenia that can accentuate a bleeding disorder. Additionally, Inflammation due to the autoimmune response in the endothelial lining of the blood vessels in the far reaches of the human body can lead to vascular impediments and devastating harm.
In regards the vaccine escape we find when looking at the efficacy of the vaccine which is proposed as a Relative Risk Reduction of 95% that the actual data used for the EUA perhaps need to be reviewed with a critical eye on the actual numbers rather than percentages. Perhaps the LNPs previously used in other past influenza vaccines have been programmed as antigen and the body destroys them on impact without the mRNA ever being engulfed into the cell to do its magic deed. Perhaps the RNA Spike has become lax during storage i.e. change in temperature, delay in use etc. or other reasons and is no longer able to withstand the rigors of binding precisely with the RBD site on the human cell. This theoretical argument is not to be taken as a glance at the vaccination itself, for we believe in the importance of vaccines, but we also believe where the science leads us. In this case 70% of the vaccinated people in Israel reported infection with the SARSCoV2 virus following the vaccination. The matter is of serious concern for the vaccine developers to find out the reason why and how to mitigate such an escape. Is the escape a nonfunction or is it creating a gateway for the virus to the cell unchecked?
Such discussions need to happen, and all ideas entertained with seriousness. All our lives, and our futures rely on such discourse.
Major Vaccines in use and in the works:
BioNTech/Pfizer/: BNT162b2, A modified mRNA-in-lipid-nanoparticle vaccine, expressing a modified S protein.
Moderna: mRNA-1273. A modified mRNA-in-lipid-nanoparticle vaccine, expressing a modified S protein.
Oxford/AstraZeneca: AZD1222, aka Oxford–AstraZeneca vaccine, Covishield, or ChAdOx1 nCoV-19. A viral vector vaccine, expressing the unmodified S protein.
Janssen/Johnson & Johnson: Ad26.COV2-S aka JNJ-78436735. A viral vector vaccine, expressing a modified S protein.
Novavax: NVX-CoV2373. A protein subunit vaccine containing a doubly modified S protein, using a special ‘adjuvant’.
Other References:
https://berthub.eu/articles/posts/genetic-code-of-covid-19-vaccines/
https://berthub.eu/articles/posts/reverse-engineering-source-code-of-the-biontech-pfizer-vaccine/
Acknowledgement:
Jaclyn Hord
