The Science Behind the COVID-19 Vaccines

Photo Credit: M-Foto/Shutterstock: COVID-19 vaccine on a laboratory bench.

Photo Credit: M-Foto/Shutterstock: COVID-19 vaccine on a laboratory bench.

By Noelle Woodward

2020 has been an arduous year for us all, with the most notable event being the pandemic that has claimed nearly 300,000 lives as of mid-December in the U.S. Scientists around the world have been tirelessly working to design and create a fast, safe, and effective vaccine in attempts to end this fear-filled time of change and uncertainty. Though traditional vaccines take years to develop, scientists have discovered a new opportunity for vaccine advancement through mRNA technology. 

Recent statements from two pharmaceutical companies, Pfizer and Moderna, reveal that their mRNA COVID-19 vaccines have been 95 percent effective in preliminary trials, introducing us to all the possibilities of mRNA vaccines and the dangers and benefits they possess. 

Messenger RNA, or mRNA, is a nucleic acid that carries the genetic instructions to produce DNA particles and proteins. 

“It has a couple of known features,” said Dr. Marica Grskovic, a molecular biologist who studied RNA translation at the European Molecular Biology Laboratory in Heidelberg, Germany. “At the end of it is a polyA tail which is a bunch of adenosines [one of the chemical “letters” that make up RNA] in a row. This is the structure that is recognized by translational machinery in our cells that make proteins from it. So each mRNA will code for a specific protein based on the nucleotide sequence that it carries.” 

Unlike traditional vaccines that work by injecting a weakened or small, non functioning part of the virus into your body used to create a reaction from your immune system that builds antibodies, mRNA vaccines use synthetic chemicals and enzymes to make up mRNA that is derived from those specific spike proteins on COVID-19 cells. 

These mRNA proteins are encased in fatty cells called lipid capsules that allow our body to accept the vaccine. 

“They work in a nutshell by hiding [in] the human cell, by pretending to be human mRNA, so that they can get in the cell and they're not rejected and recognized by the immune system,” adds Dr. Grskovic. “Once they’re in, they take possession of this translational machinery, and they make viral proteins.” 

Our immune systems then produce antibodies in response to these viral proteins, building up the immune response to the actual COVID-19 virus. 

Both of the leading mRNA vaccine candidates, the pharmaceutical partnership between U.S. Pfizer and German BioNTech as well as the government funded biotechnology company Moderna, have succeeded in reaching 95% effectiveness in their vaccine trials of this technology. 

Although they possess broad similarities in success rates, Pfizer and Moderna’s vaccines differ in molecular structure as well as transport and handling capabilities. 

“For Pfizer, the thing that's really key is that for long-term storage it needs to be at -70 degrees Celsius,” said biology teacher Maria Luca. “That’s a pretty extreme request for different parts of the country. [...] Moderna, (which only needs to be kept at -20 degrees, is) refrigerator stable, and that's really, really important for shipping and getting the vaccine to different areas.” 

Despite the extensive amount of research in the last year, mRNA vaccines are relatively new technology. Research began during the 2014 Ebola outbreak, when populations all over the world realized that we need to be more prepared for emerging epidemics. 

As with any new technology, widespread doubts have developed over safety, effectiveness, and potential side effects. As of now, the mRNA vaccine candidates appear to be very safe, and their 95% effectivity rate proves reliable even in small trials. Even the side effects will likely be consistently lower than those of traditional vaccines. 

“mRNA is like a temporary copy,” said Luca. “Because it's so temporary and so fleeting, there's less potential side effects for mRNA vaccines.”

The only uncertainty left is over how long these vaccines will actually last in the human body. It is not yet known if we will need to get revaccinated often in a matter of months, or if the mRNA vaccines will be long-lasting and we can go years before revaccinating. 

Both the Pfizer and Moderna vaccines have already been identified as requiring two shots to build up the immune response effectively: 21 and 28 days apart respectively. 

“One of the things they initially tried was a higher dose of the mRNA on some of the initial tests, and that initial higher-dose led to an extreme fever and [other extreme symptoms],” says Luca. “They had to lower it by over half for that sort of thing, and so over half then means that there's going to be an initial immune response, but that second immune response is what you’re trying to build up and train the body for.” 

In spite of these unknowns, this introduction to  mRNA technology has opened the door to many new benefits, most notably the speed at which vaccines can be produced. Though the process of creating a vaccine typically takes years, Moderna was able to design one in 32 days due to the relative simplicity of the mRNA process.

The months between Moderna’s first 32 days and now haven’t just been occupied by production. The additional time required for testing and revising has been a time-intensive process. 

After designing a vaccine, scientists first have to administer preclinical testing where they test their vaccines on cells and animals such as mice or monkeys. The vaccine then goes through three phases, (safety, expanded, and efficacy trials), in which it is administered to increasingly larger, regulated groups of people and compared with a placebo. The vaccine can then be put up for approval where country regulators such as the American FDA must approve it before it is sent out to the public. Both Pfizer and Moderna have applied for emergency authorization, and have been approved for public use. 

As of now, both vaccines should be ready for widespread public implementation in mid-spring, with distribution for healthcare workers and vulnerable citizens already occurring.

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