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Thursday, November 30, 2023

The mRNA vaccine explained

The Pfizer-BioNTech vaccine creates antibodies just as effectively as other vaccination methods, but with the help of mRNA technology

Messenger ribonucleic acid (mRNA) vaccines have been making headlines this past year during the COVID-19 pandemic, but what exactly are they? 

Since the development of the smallpox vaccine in 1796, scientists have been continually searching for safer and more effective ways to inoculate the population. Mildred Unti, a pharmacology PhD student at Weill Cornell Medicine, explained the several ways viral antigens can be delivered through a vaccination.

“The three main types of ‘traditional’ vaccines are live-attenuated, where the entire virus is delivered to your body with a mutation that renders it ineffective at causing disease, inactivated, where the entire virus is delivered to your body after being completely inactivated, and subunit, where just a part of the virus (e.g. spike) is delivered to your body,” Unti said.

mRNA vaccines, such as the recently approved Pfizer-BioNTech’s SARS-CoV-2 vaccine, function in the same way as all vaccines: They take a safe sample of the virus and use it to train the body to fight off infection when it gets exposed to the full virus. The novel part of mRNA vaccine technology lies in the way in which this is achieved. 

According to an article from the Harvard Medical School, “mRNA, or messenger RNA, is genetic material that contains instructions for making proteins.” The proteins that mRNA codes for can be used for nearly everything in every cell, and each virus has its own specific mRNAs which code for its own proteins to make up the virus. This is analogous to the way every person has their own unique DNA that codes for everything that makes them unique. In a sense, the mRNAs serve as the recipe for making the virus. 

SARS-CoV-2, for example, contains mRNA that instructs the cells to make something called spike proteins. Under a microscope, these spike proteins look like a little crown on top of the virus, which is why SARS-CoV-2 is called a coronavirus, or “crown-virus.” The goal of the SARS-CoV-2 mRNA vaccines is to take a synthesized piece of the virus’s mRNA, one that encodes for a unique portion of the virus’s structure, and train the body’s natural immune response to respond to those unique structural characteristics of the virus. 

The Pfizer-BioNTech vaccine uses a synthetic piece of mRNA to target the spike protein of the SARS-CoV-2 virus. When this mRNA is injected into the body, the body’s natural immune system learns to recognize these distinct spike proteins, allowing it to create neutralizing antibodies that attack these distinct spike proteins and destroy any foreign bodies matching that pattern. It’s important to note that while mRNA vaccines do prompt your body to create antibodies, “mRNA cannot integrate into the [human body’s] genome and therefore doesn’t change the body’s DNA,” according to Unti. 

While the approved Pfizer and Moderna vaccines are currently effective at stopping 95% of infections, it still remains unclear how long this immunity lasts in the body, according to Unti. 

“There are two separate questions there. One: How long can the body’s immune system maintain immunity to the viral antigen delivered through an mRNA vaccine? And two: How long can the mRNA vaccine prevent you from actually getting sick?” Unti said. “Luckily, we don’t know either. Both may be virus specific and can realistically only be determined after long-term studies after mass vaccination.”

Unti added that COVID-19 variants may also impact the efficacy of the vaccine.

“As we are seeing with the South African and Brazilian variants, SARS-CoV-2 can gain mutations that render it somewhat resistant to vaccination,” Unti said. “This means that even if your body can still elicit an immune response from the vaccine, its efficacy may be determined by the changes in the virus.” 

While the pandemic has provided the most prominent use of mRNA vaccines to date, mRNA technologies have been in development since the 1990s, according to a 2012 article published in RNABiology. However, it wasn’t until recently that advancements in genetics have made mRNA technologies feasible. 

Part of what makes mRNA technology so exciting is the virtually endless possibilities. Moderna, originally founded as a cancer therapeutics company, has been exploring other uses for mRNA technology, according to Unti.

“Moderna has pipelines for heart disease, autoimmune disorders and rare genetic diseases,” Unti said. “mRNA technology is particularly useful for gene replacement because it’s a safer, cheaper and easier alternative to traditional gene therapies and doesn’t actually make any permanent changes to the body. With current technologies, however, mRNA gene replacement is relatively limited.”

From personalized cancer therapies to infectious diseases, mRNA vaccines can safely and effectively train the body’s immune system to respond. Now that the first mRNA vaccines have hit the market and have shown their effectiveness, the pathway for subsequent mRNA vaccines has been paved. As genetic technology advances, the mRNA fantasies of the 1990s are becoming a reality and have the potential to be used for far more than SARS-CoV-2. 
Written by: Justin Weiner —science@theaggie.org


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