~~~ What is an mRNA Vaccine? ~~~

Model of an IgG Antibody Molecule Based Upon X-ray Crystallography
Heavy Chains, Dark Blue and Cyan; Light Chains, Yellow and Green; Carbohydrate, Red

Ph.D. degree Biochemistry, North Carolina State University; Post-doctoral training in immunology/immunochemistry, University of California, Berkeley. Currently: Professor Emeritus, Department of Molecular Biosciences, University of Kansas, Lawrence.

Vaccines have been around a very long time and have not only prevented deaths, but have also prevented deafness, blindness, paralysis and other conditions that may result when bacterial or viral disease occurs. Conspiracy theories abound that vaccines are harmful and cause autism. This dangerous, mistaken belief is based upon a single, small, research study by the British physician, Andrew Wakefield published in The Lancet years ago. Subsequent analysis of the work revealed that Wakefield falsified his data, and made terribly erroneous conclusions such that when Wakefield's conclusions reached the public, the wrong information led to fear of all vaccines. The Lancet eventually retracted the paper, and because of his egregious actions, Wakefield was stripped of his medical license. Please see: Research fraud catalyzed the anti-vaccination movement. Let’s not repeat history.

We no longer worry about smallpox - this virus is no longer present in the wild on earth, because so many individuals were immunized against this virus - no more hosts infected - no ability to replicate - virus disappeared. In the Americas, we no longer worry about becoming paralyzed by poliovirus - don't even think about it. The use of weakend (attenuated) strains of poliomyelitis virus - the Sabin oral polio vaccine - resulted in elimination of this virus from the Americas, and most of the rest of the world. In fact, the oral polio vaccine is usually not administered in the United States any longer, and only inactivated (not infectious) virus is now injected. Vaccines are now available to protect from the awful effect of cervical cancer. And now, with a pandemic sweeping the world caused by the SARS-CoV-2 virus, we need another vaccine to save us.

SARS-CoV-2 mRNA Vaccine
The Pfizer and Moderna Sars-CoV-2 mRNA vaccines are in the news in the fight against the Covid-19 disease pandemic, and are apparently currently being staged for distribution as soon as the US Food and Drug Administration (FDA) gives the go-ahead. Pfizer has stated that their vaccine is showing 90% efficacy (ability to do what a thing is supposed to do) in their clinical trials, and the Moderna vaccine is reported to be at least 95% effective. These results are wonderful news, given that the efficacy of influenza vaccines for the different strains of that virus, averages between 40 - 60%. So, 90% efficacy and above is a big deal.

What is SARS-CoV-2?
This designation means Severe Acute Respiratory Syndrome Coronavirus-2. The current virus that causes Covid-19 (Coronavirus disease-2019) is the second such SARS virus discovered. SARS-CoV-2 infection can lead to Covid-19 disease.

What is an mRNA vaccine?
An mRNA vaccine consists of a molecule known as messenger RNA (messenger ribonucleic acid), packaged inside a special fatty envelope; these packages are tiny, tiny fatty droplets (lipid nanoparticles). There will be many, many of these little droplets that contain individually-packaged mRNA molecules in the vaccine to be injected. Messenger RNA is a coded language that is translated by a special structure inside our cells (the ribosome), and translation of the message is required for and allows a protein to be made. Every different protein in our cells has its unique mRNA that contains the specific encoded information to make that protein, only. In this case, the packaged mRNA of the vaccine encodes the information to make a special protein, known as the spike protein, unique to the SARS-CoV-2 virus. If fatty droplets that contain this special mRNA are injected into our tissue, the fatty droplets will fuse with our cells and deliver the mRNA inside. Once inside, this mRNA will be translated by the ribosome machinery, and many copies of the SARS-CoV-2 spike protein will be made inside the cells. For those interested, here is more information about proteins: Please see: One of biology's biggest mysteries largely solved by AI - BBC News, Helen Briggs, 30 November 2020

Why Do These mRNA Vaccines that Encode the Spike Protein Require Such Low Temperatures for Storage?
This step provides stability to the vaccine and allows safe transport. Relative to Pfizer's mRNA vaccine, the Moderna vaccine apparently has a less-stringent low temperature requirement, perhaps because of the different formulation of the fatty envelope that encases the mRNA.

Why is the SARS-CoV-2 Spike Protein Important?
In order for any virus to cause disease, the virus must first be able to enter a living cell. Otherwise, the virus cannot make more virus - it must use the cell's intricate machinery to make copies of itself. In order for a virus to enter a cell, a structure or structures on the surface of the virus - a type of "hand" unique to each kind of virus, must recognize and grab a doorknob - a structure on the surface of the healthy cell - recognized only by that virus "hand." SARS-CoV-2 virus expresses many, many spike proteins protruding from its surface - many, many of its "hands." The spike protein binds specifcally to a protein on the surface of our cells - the doorknob - and allows entry of the virus and the release of virus genetic material inside our cells (the cytoplasm). This protein on our cells is the Angiotensin-Converting Enzyme 2 receptor (ACE-2R) - this structure binds angiotensin-converting enzyme, but the SARS-CoV-2 spike protein hijacks this doorknob, binds to it, and the virus is brought into the cell. Once inside our cells, the virus uses the cell's machinery to make thousands of copies of itself. These new virus entities leave the infected cell, and many will infect adjacent, healthy cells, etc., etc. In the process of viral replication and subsequent release, the release of new virus usually kills the cells and causes tissue damage. If specific organs are particularly damaged such as the lungs, heart, or brain, very serious complications can occur and as has occurred with this virus, caused over 1.47-million deaths worldwide and over 267,000 deaths in the United States as of November 30, 2020.

How Do These Vaccines Result in Immune Protection from SARS-CoV-2?
One arm of our immune system constantly surveys our tissue cells. What is this defense system looking for? The system is looking for foreign material shapes speckled on the surface of our cells, in combination with inherited proteins that hold the pieces. A successful mRNA vaccine is dependent upon the following: A portion of every protein of the thousands of proteins made inside of our cells, is destined to be broken into pieces - these pieces are held by special, inherited structures (histocompatibility proteins) - and displayed on each cell surface. The immune system within each of us has developed as we grow and mature, to specifically recognize each of us, uniquely, by the three-dimensional shapes of these pieces of protein AND simultaneously, the three-dimensional shapes of proteins holding the pieces, the histocompatibility proteins. This combination of shapes will be unique to each individual, and displayed on the surface of each of our cells. It is for this reason that successful organ transplants from genetically incompatible individuals are difficult, and why similar transplants between genetically-identical twins are much more likely to be successful. In essence, our immune system “sees” parts that are unique to ourselves displayed on our cells, and leaves the cells alone. Sometimes, this recognition system errs during development, recognizes some of our displayed shapes as foreign, and the result is an autoimmune disease.

Understanding the mRNA Vaccine
The vaccine mRNA in this instance is the language of the SARS-CoV-2 genetic material that only represents and is translated into the spike protein of SARS-CoV-2. As previously mentioned, the spike protein is the structure on the surface of the virus - the "hand" - that binds to our cell and allows entry (infection) of the virus into the cell. This virus RNA is made in the laboratory to EXACTLY copy the sentence within the virus’s entire genetic material of sentences that represents spike protein only, and also to contain information that allows the cell’s ribosome machinery to translate this information into virus spike protein. Recall that a portion of all proteins made inside a cell is degraded, and pieces are displayed on the surface of the cell expressing the protein. This SARS-CoV-2 spike protein mRNA is delivered to cells by injection, the mRNA enters the cytoplasm, associates with the ribosome, and is translated into spike protein - some of these spike protein molecules are broken into pieces (by enzymes), and these pieces displayed on the cell's surface. If interested in enzymes, please see: What the Heck is an Enzyme?

The immune system reacts to the appearance of these foreign shapes that are associated with histocompatibility proteins on the cell's surface, and will make antibodies (unique proteins that bind shapes) that circulate within the blood to all parts of the body against shapes unique to the spike protein. The identical three-dimensional shapes of the pieces of spike protein, will also be present on the complete spike protein protruding from the surface of the virus. Consequently, circulating antibodies will bind to the same shapes on the virus and in doing so, prevent the spike protein "hand" from grabbing the doorknob on a healthy cell - thus preventing infection, and eventually helping completely eliminate the virus from the body. Too, the response in this instance to the mRNA vaccine, is highly likely to also result in activation of special immune cells known as cytotoxic T cells. These cytotoxic T cells will recognize the spike protein shapes displayed on the cell, multiply in number over time, and will kill this cell and any cell expressing spike protein shapes on the surface. The loss of cells will be limited to those that have the mRNA delivered to them. Once immunity is established, the antibody-producing cells and cytotoxic T cells will divide and populate our spleen, lymph nodes and elsewhere, and remain poised to respond for a very long time - perhaps years. Consequently, were we to later encounter a dose of live Coronavirus, the virus would infect some cells, the cells would display all kinds of virus protein pieces, but importantly, would display pieces of spike protein and we would almost immediately generate an immune response against the virus. Therefore, both antibody-producing (B) cells and cytotoxic (T) cells will respond to any cell that is infected by the real Coronavirus, and block further infection, and/or kill the infected cell - thus stopping replication of the virus within us, and eliminate the virus altogether. The cytotoxic T cell response may occur in less than two hours. This rapid recognition prevents viral spread and limits tissue damage. Whenever we survive a viral infection or receive a vaccine against a virus, it is in these ways that our immune system responds and protects us from re-infection by the same or similar virus. If interested in antibodies, please see: What the Heck is an Antibody?