On December 7th, 2020, the first Pfizer Covid-19 vaccine was administered to a 90-year-old lady in Coventry, United Kingdom. Since then, humanity’s arsenal against the virus has grown substantially. By March 15, 2021, vaccines from Johnson & Johnson, Pfizer, and Moderna have been approved by the Food and Drug Administration (FDA) for emergency use authorization within the United States. Among the three vaccine providers, both Pfizer and Moderna utilized a brand new form of technology known as mRNA vaccines, while J&J opted to develop a traditional viral vector vaccine. But what are mRNA vaccines? How are they any different from the ones we’ve had already?
Conventional vaccines function by introducing disease-causing agent fragments to the human immune system. Attenuated (or weakened) disease agents, synthetic surface proteins, and chemicals produced by bacterias or viruses can be injected into the human body to induce an immunization memory. However, mRNA vaccines don’t contain any of the elements above. To understand the underlying mechanisms of these vaccines, we need to first dive into the foundations of cellular biology.
mRNA stands for “messenger ribonucleic acid,” and it is a naturally occurring cellular molecule essential to the cellular process known as the central dogma of biology. The central dogma of biology describes the production scheme of all crucial cellular components. Deoxynucleic acid, also known as DNA, is the heritable material that codes for all materials needed by life. However, cell machinery cannot directly read DNA, and an intermediate is required to relay information. During the process known as transcription, mRNA molecules are produced using DNA as a template. The mRNAs will then be used as the blueprint for the production of proteins. mRNA vaccines exploit this process and hijack the innate protein production system in human cells. The Covid-19 mRNA vaccines contain the blueprint for a spike protein unique to the SARS-CoV-2 virus. When these mRNA molecules are introduced into the human body, some cells will take in the mRNA and begin to construct the spike proteins. A special kind of immune cell known as the dendritic cells will then display the Covid-19 spike protein on its surface and recruit other cells needed for an immune response. Essentially, mRNA vaccines show the immune system what the pathogen looks like by teaching human cells to construct the pathogen’s defining features from a blueprint.
Traditionally, challenges in mRNA molecule delivery and stability have greatly limited the effectiveness of the mRNA vaccines. mRNA molecules are unique to the cellular environment, and any mRNA molecules detected in the bloodstream or the lymph are treated as foreign materials and degraded. If the mRNA doesn’t reach the target cells, then no immune response will occur. In recent years, technological development in delivery systems has made the concept of mRNA vaccine viable. The most efficient mRNA delivery system so far utilizes lipid nanoparticles as a vehicle for mRNA molecules. The lipid particles shield the mRNA from degradation and transport them to their target locations. After that, an immune response will be facilitated by the protein product of the mRNA.
The mRNA vaccine has two significant advantages that make it highly effective in combating a new pandemic like the Covid-19.
First, the design of a novel mRNA vaccine requires far less time than a traditional vaccine. As mentioned earlier, mRNA vaccines only contain the genetic information of specific pathogen proteins. Genetic sequencing of any unknown virus can be conducted within weeks. After that, mRNA molecules can be packaged into the existing delivery system, and the vaccine would be ready for clinical trials. In comparison, a typical development timeline of traditional vaccines can take an upwards of 10 years.
Second, mRNA vaccines are easier to manufacture. Growing viruses and microorganisms on a large scale are both time-consuming and challenging. Maintaining appropriate living conditions and removing contaminants from the living organisms make production scaling a troubling task. On the other hand, mRNA molecules can be easily synthesized from commercially available proteins and chemicals. Notably, the mRNA vaccine production scheme involves no animal components, has a low possibility of contamination, and lacks the need to grow plague cell cultures. In other words, producing mRNA vaccines is like building a new car with an existing car production line. At the same time, traditional vaccine production is like growing a recently discovered plant.
Despite the advances in mRNA vaccine, there are still several obstacles preventing the widespread usage of the new technology. Recently, the Astrazeneca mRNA Covid vaccine was believed to contribute to at least 15 deaths in Europe, and many countries have suspended its administration. Reports of blood clots and edema have been filed in some research regarding different kinds of mRNA vaccines as well. Safety remains to be a top concern for this new tech.
Furthermore, logistics regarding mRNA vaccines proved to be challenging. mRNA molecules and their delivery system are highly delicate. As a result, the storage of the vaccines requires -70 Celsius refrigeration. The need for refrigeration substantially increases the cost of transportation and storage. Large-scale distribution and administration of the vaccine could be a troublesome task for less-developed countries and regions.
Lastly, like any new technology, trust needs to be gradually established in the population. A recent survey showed that only 47% of the American people were willing to receive a dosage of vaccines if they are offered within the same week. Considering that the United States is currently experiencing the highest number of COVID cases worldwide, substantial efforts should be dedicated to reducing the stigma around mRNA vaccines and addressing the public’s concerns.
As millions of Covid vaccine doses are administered all over the world, the pandemic that has haunted us for over a year might be finally fading away. As we recuperate our strength, we must be prepared for future outbreaks. With its promising potentials, the mRNA vaccine might be the best weapon that we have against the next big pandemic.