OPINION: The art and science behind mRNA vaccines, and why it marks the start of end of pandemic


This is how the end of the pandemic starts —with mRNA vaccines beating others to arms. One of them, the Moderna vaccine, was reportedly developed in less than 48 hours. Another mRNA vaccine by Pfizer is now approved in the UK. It is readying to go into arms next week and pending expected US approval.

But what is it about these vaccines and not others that can spell the end of the COVID-19 pandemic? How can something developed in 48 hours be safe to inject into your body? Can they really be over 90 per cent effective when just months ago scientists were saying they would be happy to have a 50 per cent to 70 per cent effectiveness if it could be attained? Does any of this make sense?

It turns out it does.

We are looking at perhaps one of the greatest human achievements and certainly a candidate for the greatest developments of modern medicine. It is a combination of science and art that is based on long and complex research dating back decades, but that makes it possible to engineer the genetic code to produce only the virus’ spike protein so the cells make it and so the immune system produces antibodies to it.

With the specific antibodies in its arsenal, the body is ready to pounce upon the real virus when it attempts to enter your healthy cells.

You have seen photos of the virus. It is covered with these spikes. After receiving the mRNA vaccine doses, the body is ready and waiting for those corona spikes.

That is the science.

Here is the art.

The engineered mRNA acts like a virus, but instead of instructing the production of proteins that make you sick, it delivers the recipe for making the protein that will save your life. After the protein is made, the cell breaks down the vaccine, but now it the cell can identify the new protein, and the immune system, recognizing it does not belong there, makes antibodies to build an immune response, just as it happens in natural response against COVID-19. Except in this case, the body will build a reservoir for when the real attack comes.

It is a new approach to vaccines, skewing the injection of the neutered actual virus as in traditional vaccines. It is a leap worth further appreciation, along with a more detailed exploration of how it works.

Let us begin by understanding what a virus is and how it makes you sick.

Each human cell is like a busy city, a New York of sorts, with some 60,000 types of proteins going places, doing the work that it takes to keep your body functioning and alive. Information for how to make more of those proteins and how to make the cells of your body is kept in a “secure vault” in the nucleus of the cell, that is your DNA. It does not leave, lest it be compromised along the way and make you sick.

Instead, a messenger strand of a cousin molecule, RNA takes the role of messenger — mRNA — to deliver the code to your cell’s ribosomes, the organelles responsible for manufacturing the proteins in your body.

For the most part, your cell’s information highway is a one-way street: DNA to mRNA, to ribosomes which make the proteins you need to make the cells that make you.

A virus is a rogue strand of RNA that injects itself in that one-way street, replaces the code being carried by your body’s mRNA with instructions on how to replicate more of the virus. That changed process makes different proteins which kill the cells and make you sick.

Coronaviruses have a structure with several spike proteins, like those a crown would have, and they make the distinctive “corona” you see in depictions of the virus. By the architecture of its spikes, the SARS-CoV-2 virus that causes COVID-19 is a betacoronavirus. The spikes are literally the keys that allow the virus to open their way to invade your cells.

Though the virus infects you by entering your healthy cells, COVID-19 spikes have a preference for latching themselves to cells in lower airways and lungs, leading to pneumonia.

The body’s main defence, besides T-cells and interferons, is through antibodies which can recognize the virus and remove it by binding to it, neutralizing it, corraling it with more of the viruses, and make them attractive to kamikaze cells called phagocytes that eat them and die to save you from the attack.

Depending on the infecting dose, or the quantity of virus infecting the body, the immune system can either create enough antibodies for quick identification of the offending virus and overwhelm the infection, or enter into a battle royale for your survival. Outcomes range from asymptomatic to death.

Vaccines have typically been inactive viruses grown in chicken eggs then injected to allow the body to make the antibodies without infecting it so that when an infection occurs the body is ready to overwhelm the virus and save the day.

The danger, besides secondary side effects and adverse reactions which can range from causing other illnesses, is that the “inactive” virus manages to create a real infection.

Production has been a complex process taking between 10 to 15 years once a weakened virus, or one destroyed in a laboratory, is produced in large amounts. Because viruses mutate, growing the right strain and producing it in the millions can eat up months perhaps years of time, starting at zero and racing to stay ahead of the changing virus, every time a new strain is more prevalent.

That has been the cause of fear and skepticism about vaccines.

This is why mRNA can be designed faster, why it is safer from the standpoint of backfiring and causing the disease, and why it can be produced faster:

The mRNA vaccine concept begins by using the same medium as the virus, RNA. But instead of having a copy of the virus, its instructions are merely for the cell’s ribosomes to build the spike protein of the coronavirus, a harmless, tiny part of the deadly virus. When it is introduced into the body, it acts as the virus would; but in instructing the cell to produce the benign protein, it causes the immune system to produce antibodies that prepare the cell to fend off the real virus when it comes. Once the task is performed, the cell dissolves the instructions.

By their very nature, mRNA vaccines can be developed within days rather than weeks, whether the president of the United States leans on the researchers or the market demands it.

Because no copy of COVID-19 is injected the likelihood of an mRNA vaccine causing a COVID-19 infection is zero. Because the cells themselves are making the exact spike protein in the COVID-19 virus through the mRNA instructions, the likelihood of the vaccine failing to produce antibodies by not reaching the cells, is greatly reduced. That is what is actually bearing out in the reported effectiveness levels of the mRNA vaccines that are now in the final approval process for emergency use.

That is not to say, however, that the vaccine is 100 per cent safe. There remains the evaluation of adverse effects in certain demographic sectors of the population or delayed-onset reactions and consequences such as triggering other disease processes.

Though the production process itself needs no virus and it is a simpler synthetic method that lends itself to faster production of millions of doses, it is the job of agencies like the US Food and Drug Administration (FDA) and the Medicines & Healthcare Products Regulatory Agency (MHRA) in the U.K. to evaluate the potential risks.

On Wednesday, the MHRA in the UK granted a temporary authorization for use for the COVID-19 mRNA vaccine developed by Pfizer and its vaccine partner BioNTech of Germany based on data that showed an efficacy rate of 95 per cent and on the companies’ Chemistry, Manufacturing, and Control (CMC) data.

This constitutes the first worldwide authorisation for the mRNA COVID-19 vaccine. To date, no mRNA vaccine of any kind has been approved in the US, though the FDA is currently reviewing the request for an Emergency Use Authorisation (EUA) from Pfizer and Moderna under heavy pressure from President Donald Trump to speed up the process.

Shots also going into arms next week are of Russia’s Sputnik V vaccine, the world’s first registered adenoviral vaccine approved by Russia with reported efficacy of 91.4 per cent after trials in India, Venezuela, Belarus, and the UAE. Adenoviral vaccines use an empty viral vessel unable to reproduce itself to deliver a gene of a portion of the virus to the cells in order to spark antibody production.

“Today’s Emergency Use Authorisation in the U.K. marks a historic moment in the fight against COVID-19,” said Albert Bourla, Pfizer chairman and CEO.

In addition to the EUA request at the FDA, a Pfizer statement said Wednesday the companies “have submitted the final Conditional Marketing Authorisation Application (CA) following rolling submissions with the European Medicines Agency (EMA) and several other regulatory agencies around the world.”

Leave a Reply