Inject the Message: Messenger RNA (mRNA) that is! Why I – an artist, social worker, and biologist – am so excited about mRNA-based COVID-19 vaccines, beyond just the hope of ending this pandemic.

February 7, 2021

Yes, I’m missing love, life, and connection in real life. And my goddess – the theatre! I’m one of the lucky ones. When my performance-art-focused photography business began to crumble at the onset of this pandemic, I was able to beef up my Jefferson Patient Outreach and Adherence duties in the HIV clinic, as well as get another small job in a beloved lab I worked in for well over a decade. The clinic brought me early offerings of Pfizer’s mRNA-based COVID-19 vaccine. As I hear many do, I teared up with joy when receiving that first injection along with my clinic colleagues. But those happy tears were not just for excitement and hope that these vaccines will accelerate the return to more life IRL (and less death and hardship), but also that even bigger history was being made with that message flowing into my arm.

 As a molecular biologist, I’ve worked in an HIV lab intermittently since way back in 2002 when I was a college kid. I believe this is the dawn of a new era in vaccinology, and beyond. This long-studied concept of using mRNA to prime our immune system to fight disease has overwhelming potential to fight not just our current pandemic, but pretty much any microbe, and also other diseases like cancer. Unfortunately, history (as well as the plethora of misinformation that’s out there) has given many people countless reasons to experience vaccine hesitancy. However, when considering the striking data, and pondering theories and methods of various vaccine platforms, mRNA technology really looks like a winner. An elegant, efficient route to safely elicit a robust immune response.

Bio 101 refresher: Aside from water and fat, we are made primarily of protein. Proteins are macromolecules required for all structure, function, and regulation of pretty much everything our cells/tissues/organs/bodies do. These macromolecules are made in a two-step process, which is known as the central dogma of molecular biology: DNA -> RNA -> Protein. First, in the nucleus where our DNA resides, transcription occurs. This is the step of transferring our genetic instructions from DNA to mRNA. mRNA then leaves the nucleus to go out to the cytoplasm, where it is converted to protein in a process called translation. 

No matter the platform, all vaccines essentially provide a gentle way of introducing components of a pathogen to our highly evolved immune systems. This gives our bodies a chance to recognize the foreign elements (and/or the whole weakened or dead pathogen) and respond to the real one if it invades in the future. Pfizer and Moderna’s vaccines have two main components: 1. mRNA (encoding SARS-CoV-2 spike protein) which is encapsulated by 2. lipid nanoparticles. In other words, these vaccines are like little fat bubbles with instructions inside to make the coronavirus spike protein. Following a vaccine injection, immune cells encounter the vaccine particles and absorb them. This then frees the mRNAs into the cytoplasm inside the cell where it can be converted into the spike protein. The spike then presents itself to the surface of the cell. The immune system subsequently sees this protein, recognizes it as foreign, and builds up immunity in multiple ways. If the vaccinated individual later encounters the actual virus, it recognizes the virus’s spike (on the surface of the virus) and then stops the invader in its tracks.

What are the advantages of mRNA-based technologies? Well, relative ease, efficiency, and speed. These are some of the reasons that mRNA vaccines have been ahead of the pack. Unlike other platforms – subunit, killed and live attenuated virus, and DNA-based vaccines - all we need is the genetic sequence of the virus of interest, and to determine the target antigens. Then, mRNA encoding for the chosen antigen(s) can be synthesized! We can thereby avoid wasting time growing viruses (or parts thereof), and circumvent concerns about growing vaccine components in cell culture. Plus, the potential for anti-vector immunity* is avoided. This all streamlines the science and production – saving time, resources, and potential complications. If a mutating virus requires updated antigen targets, this platform would be more suited towards pivoting to new booster shots targeting evolving strains. mRNA-based boosters are already in the works to preemptively target new SARS-CoV-2 variants. 

Since mRNA is “genetic material” – can it alter our DNA? Nope, it’s virtually impossible, and unfortunate that so much misinformation is out there erroneously suggesting otherwise. According to worldwide vaccine expert Dr. Paul A Offit, we have a “a greater chance of becoming spiderman after being inoculated with this vaccine” (than it altering our genome). This is because mRNA cannot do any of the following, which would be all required to change our genome: 1. enter the nucleus where our DNA resides; 2. be reversely transcribed to DNA; 3. integrate into the host cell genome. Additionally, mRNA is not very stable on its own (hence the ultra-cold freezer requirements you’ve heard about) and is naturally degraded by normal cellular processes after it does the job.

How can we trust Operation Warp Speed? The science for these vaccines has inadvertently been underway since 2003 with the onset of the SARS pandemic. SARS (severe acute respiratory syndrome) is caused by a coronavirus called SARS-CoV. You can tell by the name that this virus is extremely similar to that which causes COVID-19 (SARS-CoV-2). So, mRNA researchers were well on their way to starting clinical trials just a few short months after the genetic sequence of the new coronavirus was in hand. However, fast-development phrasing and messaging – the vaccine race, warp speed, etc – can understandably sound scary. Until I saw the shockingly fantastic safety and efficacy data with my own eyes, I was a bit skeptical myself. Most scientists wouldn’t have even imagined that we’d be this far with not one, but two vaccine options by this time – and with 94%+ efficacy! But luckily here we are, and the science has not skipped any steps. On the other hand, what’s been accelerated is the blazing through logistical barriers and bureaucratic roadblocks. With all eyes on this virus, and billions of dollars thrown at the vaccine industry, fundraising and recruitment for clinical trials was no longer slow as molasses, and quite the contrary! For once, there were too many volunteers. Additionally, the FDA focused on and fast-tracked applications and paperwork. A lot of luck was also involved. mRNA research has made huge strides in recent years, and it matured just in time for our pandemic.

I’m young and healthy, why do I need a vaccine? We all need to do our best to avoid contributing to the infection chain. Protect your community! The more bodies that house the virus, the more it will have a chance to evolve, and the higher the odds of it becoming more dangerous, as we’re already seeing. More infectious variants lead to more infections and therefore deaths, whether or not the death rate increases. Even if statistically speaking it looks like one has good chances to fight COVID-19, the long-term effects are still largely unclear. Those with chronic COVID syndrome (aka “long-haulers”) can suffer from an overwhelming and debilitating list of symptoms. And many otherwise healthy young people who were infected, with seemingly minimal symptoms at first, are returning later to their doctors with new chronic issues. Plus, preliminary data is showing that all covid-19 vaccines appear to lessen asymptomatic (and presymptomatic) spread. So, the more people who get vaccinated, the faster we can return to “real life”.

You sold me on mRNA - should I forgo other vaccine options (if available) in favor of the mRNA variety? No! The best covid-19 vaccine is the one you have access to first. Time is of the essence, and only time will tell how these various technologies compare to one another. The best thing to do for the safety of you and your community is to accept whatever option you are offered when you qualify, and inject that vaccine ASAP!

* Some vaccines utilize viral vectors, which are genetically altered viruses used as tools to deliver genetic material in a safe manner that does not cause illness. If the body has seen that particular vector before, or a very similar one, the immune system may remember and clear it before the effect of the vaccine has a chance to work.