The Science Behind Major COVID Vaccines Will Lead to Faster Manufacturing

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The fate of the COVID pandemic may well be dictated by a biological element several hundred nanometers long.

Messenger RNA, or mRNA, is at the heart of the two main vaccine candidates, one from Moderna and the other from Pfizer and partner BioNTech. The companies’ clinical trial data suggests that these vaccines are around 95% effective. And Pfizer’s vaccine, which has already been given the green light in the UK, could start distributing to some Americans in just a few weeks.

It will be a distribution challenge and a vaccination campaign like the world has never seen. But as remarkable as this challenge is, the science that led to the creation of promising vaccines in less than a year is equally remarkable – a process that usually takes around five years or more. And in the case of Pfizer and Moderna vaccines, their pioneering technologies could make it much easier to expand the manufacturing process.

So how is a vaccine made, anyway? And how did academic institutes and pharmaceutical companies succeed so quickly in the midst of a pandemic?

How a virus gives birth to a vaccine

Medicines don’t just spring from nothing. Creating one, whether it’s a therapy to treat a disease or a vaccine to prevent it, is a fascinating process that begins with a thorough examination of the biological enemy in question.

“One of the first steps in making a vaccine is to identify the weak point of the pathogen; to identify the vaccine target, ”says Peter Hotez, dean of the National School of Tropical Medicine at Baylor College of Medicine in Houston.

The fundamental role of a vaccine is to induce an immune response, which will then offer protection against a pathogen by forcing your body to create antibodies that attack antigens, the components of a pathogen that produce the immune response. So when the virus itself knocks on the door, your body already recognizes the intruder and can deploy its arsenal of antibodies.

Many common vaccines contain small pieces of the virus or the bacteria itself which were killed after being grown in a laboratory or are alive but severely weakened and are therefore unlikely to make you sick.

In the case of the coronavirus, identifying the “weak spot” Hotez referred to was the crucial first step. It’s something rather sinisterly called spike protein.

“When you think of the coronavirus, everyone has seen the pictures of the virus which has the colored spike protein, that red lump sticking out of this cylindrical viral compound,” says Dean Fanelli, partner in the intellectual property department of Seyfarth Shaw LLP in Washington, DC, offices.

Radoslav Zilinsky – Getty Images

This “spike protein” does exactly what you think a spiked object would do: it pierces something else. “The spike protein binds to the ACE2 protein found in human cells. And so we know that’s how this virus actually infects people, ”Fanelli adds.

The drug makers knew they should teach the body to attack antigens attracting antibodies to the spike protein. But the way Pfizer and Moderna have done it is very different from the traditional way of creating vaccines.

Creation of a COVID mRNA vaccine

Messenger RNA is a powerful biological tool. It’s the molecule that tells your cells what to make, like proteins.

Theoretically, this means that you can harness mRNA to transform your body cells in mini drug factories which can fight various diseases. Barely a year ago, large sections of the biotechnology community were skeptical about the use of mRNA technology to make treatments.

But that’s exactly what the major vaccine candidates have been able to accomplish. By exploiting the genetic code of the virus, which has been made available worldwide by Chinese scientists earlier this year, drug makers were able to figure out how to use mRNA to force the body to mimic the spike protein and induce an immune response.

Basically, they go back one step in the traditional vaccine manufacturing process. Rather than injecting the surface proteins that wake up the immune system directly into the body, Pfizer / BioNTech and Moderna inject the RNA that codes for these proteins.

One person who has been a staunch RNA vaccine evangelist is Phil Dormitzer, who happens to be the vice president and scientific director of Pfizer’s viral vaccines unit.

“I’ve been thinking about RNA vaccines for a long time,” he says. “Things really came together in 2018 when we agreed with BioNTech to launch the new mRNA program.” This collaboration started as a quest to develop an mRNA-based influenza vaccine. The focus changed once the pandemic hit.

Dormitzer cites two specific reasons he is excited about the technology: the flexibility and the ability to quickly manufacture and expand treatments. He explains that with RNA vaccines, an immune response could produce both antibodies and T cells, another key immune system warrior, which is important because either one might be more effective against COVID.

The second reason is particularly critical at a time when these vaccines must be scaled up massively for worldwide distribution.

“I think a lot of people are drawn to mRNA because you can make a piece of mRNA in a day, right?” said Hotez of Baylor. “And there are companies that you can outsource that will make the mRNA for you.”

Unlike more traditional vaccines, you don’t have to spend months and months manually harvesting and purifying antigens from a pathogen to make the final product. You can simply let the mRNA sequences with instructions get lost in the body. After that, the body’s cells do the heavy lifting on their own.

This is one of the reasons why Pfizer and Moderna’s vaccines may have outstripped their competition in regulatory terms – and what could help them ramp up to hundreds of millions of vaccine doses by the end of this year. 2021.

An army of COVID vaccines

Ultimately, conquering the coronavirus pandemic is likely to require a motley team of vaccines using different technologies. Not everything will be an mRNA vaccine.

For example, Hotez’s own group worked on a COVID-19 vaccine that uses a much more traditional technology called recombinant adenovirus technology.

“We started making the new spike protein like other groups did,” he says. “It’s just that different groups are using different technologies to do it, whether it’s mRNA or. And each of the technologies has strengths and weaknesses. “

For Pfizer, one of the more complex issues is the ultra-cold temperature its COVID vaccine needs for storage, around 70 degrees Celsius negative. This is precisely because of the mRNA component of its specific vaccine, which could break down without being completely frozen. Pfizer even had to create a special high-tech storage and transport case to face this exact dilemma.

So, although mRNA vaccines have some issues, the speed they provide is exactly what we need right now. Distributing the COVID vaccines and persuading people to get them will be the next big challenge – and there are still many more pioneering projects to come during this pandemic.

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