mRNA Vaccines: The battle against the SARS-CoV-2 pandemic

2020.

It was supposed to be the beginning of a new era. We all had so many plans. Think back to where you were one year ago (Feb 2020). Maybe you were lamenting the untimely demise of your New Year’s resolution to eat more vegetables. Perhaps you were at vegan brunch, cheek to cheek with friends, or maybe visiting local vendors at Farmers markets. The only viral thing  in your life was the astounding feat of South Korean filmmaker Bong Joon-Ho, whose non-English film Parasite had won Best Picture at the Oscars. Viruses, videoconferences, and vaccines weren’t even in your mind, much less a part of your day-to-day life.

Getting back to that life requires an effective vaccine against SARS-CoV-2, the viral agent that causes COVID19. Vaccines are one of our greatest medical accomplishments. Take smallpox for example. Prior to eradicating smallpox through aggressive global vaccination campaigns, 30% of those infected died leading to 300 to 500 million deaths in the 20th century alone. Vaccines have saved countless lives and improved the quality of so many more. While the science behind vaccines can be complex, the concept is straightforward. At its core, vaccines are a training exercise for your immune system. 

Military training exercises split a unit into two teams to practice drills against each other. Both teams get the training they need to fight the real threat even though neither opposing team is the real enemy. Vaccines against SARS-CoV-2 play the other team to our immune systems. They contain a part of the virus and mimic a real threat, which trains our immune systems to fight better. 

Pfizer and Moderna produced the first approved vaccines against SARS-CoV-2 and both use mRNA vaccine technology. mRNA, or messenger ribonucleic acid, is a format of information much like DNA, or deoxyribonucleic acid. DNA is an information storage system and contains all of our instructions. It is our operator’s manual- kept secure within the nucleus in our cells- much like a data storage unit locked up in the server room in a building. When a specific set of instructions are needed, you can copy the respective file onto a USB drive from data storage and take it to your office somewhere in the building for use. mRNA is the USB drive – mRNA contains only part of the instructions for carrying out the needed task in our cells.

How does the vaccine work?

Usually, researchers and manufacturers produce the components of viruses or bacteria that go into vaccines, also known as antigens, in labs or various manufacturing facilities. mRNA vaccines differ from traditional vaccine platforms by not containing the actual antigen. As described above, mRNA is essentially a set of instructions for our cells. Vaccines containing mRNA hack this cellular process by providing instructions to our cells for making the antigen. During vaccination, the mRNA fragments are injected into our arms. They are able to enter our cells and into our cytoplasm where they provide a blueprint to produce the message with our own translation machinery. 

The message in the vaccine encodes the spike protein of the virus, which the virus uses to enter and infect our cells and cause disease. These mRNA vaccines contain only the RNA encoding the spike protein. The vaccine cannot infect someone with the virus or cause disease. The message also degrades in the cytoplasm quickly, so our cells only produce the spike protein for a short amount of time. Finally, mRNA from the vaccine cannot enter our nucleus and alter our DNA.  

These mRNA vaccines contain only the RNA encoding the spike protein. The vaccine cannot infect someone with the virus or cause disease.

Once produced, our cells display the spike to our immune system. Our immune system is constantly patrolling trying to identify possible threats. Upon recognizing the spike protein as a foreign threat, our immune system starts developing a response specifically targeting the spike protein. That response is then set for a rapid response if the threat is ever seen again. So when the vaccinated encounter SARS-CoV-2, their immune system immediately recognizes the spike protein as a threat and initiates a protective response.

So what’s in an mRNA vaccine? The mRNA Pfizer and Moderna vaccines contain: the mRNA for the spike protein, lipids (fats like cholesterol), salts, and sugar. The fats surround the mRNA fragments allowing this lipid particle to fuse with our cells. This delivers the mRNA inside our cells. The salts and sugar help to protect the integrity of the vaccine. Both the Moderna and Pfizer vaccines are nearly identical except for minor differences in the lipids used. That may be the reason why there are differences in the stability of the two vaccines and how they must be stored. Long term storage for Pfizer vaccines require temperatures between -80°C to -60°C whereas Moderna vaccines can be stored at -20°C, which has a significant impact on equitable distribution and the logistics and supply chain requirements for these vaccines.

Clinical trial data for both demonstrate high efficacies. The Pfizer vaccine reports an efficacy of 95%. To get this number, Pfizer gave 21,669 study participants the vaccine while 21,686 study participants received the placebo. Neither the participants nor the researchers were aware of which subject got which treatment, reducing the chance of bias affecting the results. After sufficient cases were reported, the researchers unblinded the study and revealed 95% of those who acquired symptomatic COVID were given the placebo. Therefore, the vaccine was deemed 95% effective against symptomatic COVID19. So far, the safety data for both vaccines seem promising. There have been very few serious side effects reported, most common being tiredness, muscle aches, fever, or chills. 

Too fast, too furious?

The fact that we went from discovering the existence of a novel virus to vaccinating people in less than a year is an astounding feat of science and humanity. It highlights the importance of foundational scientific research- decades of data and expertise on mRNA vaccine technology, our understanding of related viruses, and a global resolve to dedicate unlimited resources to the cause. Traditionally and problematically, vaccines take a long time time to develop. Limited resources, lack of incentive for pharmaceutical companies, governmental disinterest (until a crisis) and less investment by the public slow breakthroughs. The historic speed of discovery, research, safety testing and distribution should be celebrated. The global scientific community has come together to study the virus and develop therapeutics. Sharing information real time has allowed thorough scrutiny of the safety and efficacy of any treatment prior to approval. Collaborations between governments, public health workers and researchers, and scientific researchers on an unprecedented level have showcased what we are truly capable of. 

So, here’s to 2021.

Author: Rai Somshukla Chaudhuri

Featured Image:  Veronica Falconieri Hays; Source: Lorenzo Casalino, Zied Gaieb and Rommie Amaro, U.C. San Diego 

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