mRNA vaccines – a revolutionary technology to combat COVID-19.

Guest post by Talia Oates, Melbourne.

‘I felt like a god’ (1) were the words spoken by Dr Kati Kariko when her and her colleague unintentionally discovered the potential of messenger RNA (mRNA) for future vaccines. In 1989 she worked as a low-level research assistant professor, performing experiments where mRNA was inserted into cells in order to make desired new proteins. However, when observing the production of this target protein, her and her colleague noticed that there were other unexpected proteins produced. This accidental discovery laid the foundation for mRNA usage for vaccines, and despite the prescient nature of Dr Kariko’s ideas, her passion for understanding the potential of mRNA is what enabled scientists today to create successful mRNA vaccines to combat the current COVID-19 pandemic.

The safety and efficacy of mRNA vaccines is a topic of concern, as this new technique has rapidly developed. Against this, mRNA vaccines have been studied for around 10 years, in particular for viruses such as Influenza, Ebola and other diseases (2). In weighing up this record, tt is important to understand what efficacy stands for, as this word is often thrown around in the media. Vaccine efficacy refers to the percentage of individuals in vaccinated and non-vaccinated groups who contract disease, showing how well a vaccine prevents disease in a controlled clinical trial (3). Therefore, when discussing the safety and efficacy of a vaccine, the term efficacy refers to the results from the clinical trial where the vaccine was tested, not the real-world effectiveness. The effectiveness of a vaccine considers the intended outcome of the vaccine. Pfizer and BioNTech Ltd. (the pharmaceutical companies who created the Pfizer vaccine) classify effectiveness as a measure of how good the vaccine is as preventing serious effects of disease, from symptomatic illness, to severe disease, and even death (3).

But what are mRNA vaccines?
The concept of mRNA vaccines is fairly new and difficult to understand, so here is a crash course to improve your background knowledge. We all have DNA, a molecule with two string-like strands of nucleotide chemical building blocks which encode for your unique genetic heritage. RNA is another string-like strand of slightly different chemical building blocks which is a copy of the information stored in DNA strands. RNA is referred to as mRNA when it travels from the cell nucleus, where DNA is stored, to your cell’s main machinery for protein formation where it serves as instructions to make proteins.

Since mRNA is a messenger which provides precise signals your body to make proteins, scientists like Dr. Kariko believed that harnessing it would allow physicians to direct the body to produce the proteins we particularly want it to make in order to ward of disease. The use of mRNA in this way for vaccines has been a long awaited, however the recent outbreak of COVID-19 sparked rapid new developments in this discovery pathway.

An important preliminary step was work by Justin Richner, Michael Diamond and collaborators at Washington University School of Medicine, Sant Louis USA who in 2017 developed a successful mRNA vaccine candidate that protects against Zika Virus infection. Zika virus infection is a disease which severely damages the foetus of infected pregnant women(4). This vaccine was first tested in mice and involves the mRNA being delivered to subjects cells inside microscopic oily droplets that enable mRNA to enter cells (4). The discovery of this vaccine candidate for protection against Zika virus infection was pivotal for mRNA vaccine progress. Not only did it demonstrate the successful production of an effective mRNA vaccine but paved the way for other mRNA vaccines to be developed rapidly for novel diseases.

Prior to COVID-19, there were outbreaks of two similar viral diseases. These were respectively (i) Severe Acute Respiratory Syndrome (SARS) emerging in 2002-2004, and (ii) Middle East Respiratory Syndrome (MERS) in 2012 (5). mRNA vaccines were developed for these diseases, however the fortunate lack of progression to pandemic disease status halted their development. The prior knowledge of these two viruses helped rapid development of the COVID-19 mRNA vaccines we have today, most notably the Moderna and Pfizer vaccines. The function of mRNA in these vaccines is to produce a characteristic surface protein carried by the infectious virus, namely the Spike (S) protein, as it is this protein which binds to human cells and allows the virus to infect, and vaccines that effectively target this protein can protect against infection (2).

Benefits of mRNA vaccines
mRNA as a vaccination technique is often questioned by those who may not understand it. However, once the benefits are established it is quite clear why mRNA vaccines pave the way for a future armoury against new viral diseases. mRNA vaccines are advantageous as they are much easier and faster to manufacture. As previously mentioned, years of advanced research of mRNA vaccines for similar viruses such SARS and MERS has provided a platform for SARS-CoV-2 research. Additionally, the genetic code for the S protein antigen was rapidly established, enabling the production of mRNA for the vaccine to be easily scalable (5). Most of our common vaccines are protein-based and are often produced elaborate manufacturing facilities. mRNA vaccines differ as they are translated by the host cell-machinery. There are many technical and practical advantages in this process. It can be rapidly scaled up, and is easily modified to deal with virus variants.

The rapid production of mRNA vaccine candidates is another area of concern for the public. It is well known that in the past it has taken years to develop some of our most used vaccines, including the first bi-valent Influenza vaccine was produced in 1942, many years after the 1918 pandemic (6). Advances in vaccine technology over the years has allowed for such innovation as the mRNA vaccines, explaining why these rapidly produced vaccines can equally be as effective. The colossal need for a vaccine to combat the pandemic meant that sufficient investment funding was easily achieved, reducing this often-time-consuming aspect of vaccine development. As demonstrated by the development of COVID-19 vaccines, when this funding is readily available the production of effective vaccines is much quicker.

A glimpse into the future of vaccine development
The development of mRNA vaccines against COVID-19 has been revolutionary. It is evident that mRNA vaccine technology has transformed the way we approach novel vaccines, not only for COVID-19 but other diseases too. This rapid approach has streamlined the manufacturing of vaccines, allowing us to combat the threat of COVID-19. The roll-out of these vaccines to the millions of people who need and deserve protection will establish the benefits of mRNA as a vaccine technique. Despite this, community support of mRNA vaccines is essential. The success of mRNA vaccines should be reaped by everyone, and it is our duty as citizens to help educate one another on this innovative technology.