Messenger RNA (mRNA) Vaccinations for COVID-19 – History in the Making Amazing Science Gives a Ray of Hope

A COVID-19 vaccine is on the imminent horizon. It is considered the key to lifting social-distancing measures, reopening schools, markets, and events around the globe.

Vaccination is key to preventing disease and has been a major advance in public health to eradicate epidemics like smallpox or polio. Vaccines work by mimicking an infectious agent, and by doing so, train our bodies to respond more rapidly and effectively against them.

Vaccination is the most successful medical approach to disease prevention and control known to modern medicine. Vaccines has saved millions of lives. The advent of messenger RNA (mRNA) vaccines is likely another major medical milestone that we will look back on in awe.

This new class of vaccines based on mRNA is likely to be the first available against COVID-19. Companies are putting these vaccines into human tests at an unprecedented speed.

Prior to the present pandemic, mRNA technology was unproven. Now it will likely revolutionize vaccine development going forward. If an mRNA vaccine is approved for coronavirus, it would be the first of its type. It’s a novel way of making a vaccine and, so far, no (such) vaccine has been licensed for an infectious disease.

An investigational vaccine, mRNA-1273, designed against COVID-19, was recently found to be effective and safe in phase II trials according to The New England Journal of Medicine. This vaccine is now in phase III trials. Behind this vaccine is Moderna and the NIH.

What do vaccines do?

In general, vaccines “train” and strengthen the body’s immune system to develop resistance against pathogens and illnesses by imitating an infection — to kick up a natural immune response specific to the infectious agent (such as COVID-19 virus).

Specifically, vaccines work by training the body to recognize and respond to the proteins produced by disease-causing organisms, such as a virus or bacteria. Traditional vaccines are made up of small or inactivated doses of the whole disease-causing organism, or the proteins that it produces, which are introduced into the body to provoke the immune system into mounting a response.

mRNA vaccines

An RNA (ribonucleic acid) vaccine or mRNA (messenger RNA) vaccine is a new type of vaccine. mRNA vaccines essentially “trick” the body into producing some of the viral proteins itself. They work by using mRNA – which is the molecule that essentially puts DNA instructions into action. Inside a cell, mRNA is used as a template to build a protein.

As a molecule found within all forms of cellular life, messenger RNA (mRNA) is central to biology itself. It quite literally finds itself the messenger between DNA, the body’s genetic blueprint, and proteins, the molecules responsible for the structure, function and regulation of the body.

Ordinarily, the process goes like this:

mRNA is unique because it is a part of the body’s internal mechanism used to synthesize proteins. With respect to vaccines, we are taking an mRNA unit that is made in a lab and introducing it into the body. We are literally instructing the body to synthesize a protein of our choosing. Therein lies the magic.

mRNA is a cog in the wheel of the body’s apparatus for producing a huge variety of proteins that the body requires to survive. mRNA is synthesized inside of our bodies. It takes a “picture” of a chunk of our genome. That “picture” represents the “blueprint” for the synthesis of a specific protein – it is taken downstream and is the “template” against which a protein is made. The protein can be any of the millions that the body needs to function. It may be anything from muscle to a hormone (these are all proteins).

With respect to mRNA vaccines – we create a synthetic mRNA – we take an artificially created mRNA – made in a lab – and introduce it into the body. We’ve pre-programmed the mRNA to synthesize a protein of our choosing. Hence, we’ve “tricked” the body into making a specific protein based on the mRNA template that we’ve created.

In the case of a virus like COVID, the protein looks exactly like a portion of the virus. By a separate and distinct process – the body will now mount a defense (i.e. make antibodies) that will neutralize that viral particle. By a separate process, the body recognizes that protein as being “foreign” and mounts what is known as an immunological response.

To summarize, mRNA is the go-between between our DNA (our genome) and the body’s protein-producing apparatus. Proteins are the building blocks of every cell. They include antibodies, hormones, enzymes, and muscle tissue – to name just a few. mRNA is the middleman. It takes an imprint from our DNA. That mRNA imprint is then presented to the cell’s synthesis apparatus – which produces a corresponding protein.

In theory (and now in practice), we can produce mRNA that is encoded to produce a specific protein. The mRNA is introduced into the body causing the body to produce an mRNA-specific protein. That protein can “look like” a COVID viral particle. Proteins such as these are referred to as antigens.

What is an antigen?

In immunology, an antigen is a molecule or molecular structure — such as may be present at the outside of a viral particle (i.e. a component of the particle’s cell wall) — that can be bound to by an antigen-specific antibody or B cell antigen receptor. The presence of antigens in the body normally triggers an immune response.

In fact the antigen-protein can trigger the immune system to produce an immune response – including the production of antibodies which are targeted against COVID. More accurately, the protein represents only a tiny portion of the virus. But that is sufficient to cause the body to mount a defense against the entire viral particle.

If all this sounds like science fiction, rest assured that it is happening. In fact, we will soon all have access to an mRNA based vaccine against COVID.

What are the advantages of mRNA vaccine over others?

mRNA vaccines offer multiple advantages over DNA vaccines in terms of the following:

  • Mass production
  • Administration
  • Safety

As to rapid production, on January 11, 2020 – Chinese scientists posted the first sequence of the novel coronavirus’s RNA genome online. The following day, the preclinical development process began. It took less than 4 hours to complete. On April 6, Inovio began a clinical trial of its vaccine based on this information. Today Moderna is in phase III trials.

The RNA is made from a DNA template in the lab. The DNA can be synthesized from an electronic sequence that can be sent around the world in an instant by computer. Currently it takes about a week to generate an experimental batch of an RNA virus. By comparison, older technologies can take many years. Note that no actual virus is needed to make a batch of an RNA virus.

mRNA vaccines combine desirable immunological properties with an outstanding safety profile and the unmet flexibility of genetic vaccines. They are safe for a number of reasons. First, introduction of virus or viral particles into the body are no longer necessary – this is an older method. Second, mRNA stays clear of the cell’s nucleus and therefore does not get incorporated into the host’s genome.

The mRNA vaccines must pass a gauntlet of rigorous trials — proving they’re safe and efficacious. The process involves thousands of subjects/volunteers. That said – one key advantage hinges on rapidity of manufacture. This is because the process is cell-free and scalable.

A key advantage in mRNA technology is that the production facility could theoretically manufacture vaccines rapidly against multiple targets, with minimal adaptation to processes and formulation. Within weeks, clinical batches can be generated after the availability of a sequence encoding the immunogen.

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