mRNA vaccine development and related challenges

Ana Butskhrikidze

Faculty of Natural Sciences and Medicine

Genetics and molecular biology

Cort Anderson

Ilia State University

Tbilisi, 2022
 Nowadays vaccination is an important requirement to save our lives from many

different diseases that might be caused by a variety of diseases causers. Vaccines generally help

to prepare the body to fight off foreign invaders (such as bacteria, viruses, or other pathogens)

(Melief et al., 2015). Most vaccines contain a harmless part of a specific bacterium or virus that

triggers an immune response. While the mRNA vaccines work in a different way because we do

not need the disease effector itself (Pardi et al., 2018). Just having the sequence of the gene

needed to produce the mRNAs needed for producing antibodies for the effector’s antigens

(Pardi et al., 2018). The mRNA produced enters the cytoplasm of our cells and works there

without the need to enter the nucleus because it needs to reach the areas where the proteins

are translated (Joanna et al., 2004). Moreover, our immune system will do an immune response

to the structure formed from the mRNA and starts to produce antibodies so whenever the virus

affects our body these antibodies will start attacking it and defend us from the virus (Melief et

al., 2015). In this essay, I will talk about the development of the mRNA vaccine, its stability, the

mechanism of action of the vaccine, and the problems that scientists encountered when

creating the vaccine. I will also try to talk about ways to solve these problems.
Development of mRNA vaccines

Since the mRNA vaccines were discovered in 1990 till now, there are several problems

facing scientists in developing these vaccines (Knezevic et al., 2021). The stability of these

vaccines, storing them as well as the way it is delivered with.

mRNA stability

The mRNA must be produced in a safe environment so it will be stable. That problem was

resolved by several steps and discoveries. According to Knezevic et al. (2021) article. The mRNA

is easy to be damaged and degraded due to the environment of the RNase enzyme. As well as

for the innate reaction and the reduction of mRNA translation due to the mRNA

immunogenicity. According to the discovery of Karikó and Weissman using modified

nucleosides reduces the immunostimulatory effects of in-vitro-generated mRNA, which

reduced the toll-like receptors that cause the innate reaction. Furthermore, sequence

engineering was developed by Schalke and his colleagues which enable the synthesis of mRNA

without causing the innate reaction.

Storage

Due to mRNA sensitivity, the ultrasound chain is essential for the delivery of COVID-19

vaccines worldwide. A way to eliminate process developmental limitations with mRNA can help

reduce mRNA temperature requirements to a minimum. "The low temperatures required for

mRNA stabilization come from the rough edges caused by rapid development and

deployment," explains Dr. Liddell. (WHO Coronavirus Dashboard. June 2021).

Now the new covid vaccines Moderna and Pfizer have to be stored in such a cold

environment at -80°C. According to Uddin’s and Ronis (2021) article. Freeze-drying or

lyophilization is a technique used to increase the stability of the vaccines under higher
temperatures. Lyophilization is a lengthy, expensive, and time-consuming procedure, but it

benefits us very much because it helps to store the vaccines in higher temperatures without

damaging them. This process helps us to store the vaccines for 21 months at 4°C and, for 8

months at room temperature. So, we can store these vaccines in the refrigerator instead of

having a freezer which might be hard to be found everywhere and which costs much more.

mRNA delivery system

It is very challenging to inject a necked mRNA into the body, due to the high immune response

done by the body to fight that foreign mRNA (Liang et al. 2021). Our body will degrade these

foreign mRNA by nucleases. So, it will be hard to get the benefits of the injected mRNA vaccine

(Liang et al. 2021). The injected mRNA needs to reach the cytoplasm of the cell in order to

translate the protein needed (Joanna et al., 2004). To pass through the cell membrane the

mRNA must have a smaller size and it is big enough to not pass through without being coated

(Joanna et al., 2004). Furthermore, the delivery system can be divided into viral and non-viral

vectors using some lipids or polymer delivery systems (Xue et al., 2017). Due to this challenging

process of delivery, there are several ways used to deliver these vaccines. According to Liang et

al. (2021) article, He mentioned several ways that can be used (Liposome complexes,

Nanoparticles, polymers for mRNA delivery). These all helped us to deliver the mRNA in a better

way avoiding degradation and having better results.

Finally, mRNA-based vaccine technology is a promising tool for developing new therapeutic and

prophylactic vaccines against infectious diseases and cancer. However, a variety of barriers

associated with extremely large mRNA size, charge, internal instability, and high susceptibility

to enzymatic degradation impede transmission. Extensive use of mRNA-based therapies is still

limited by the need for improved vectors or drug delivery systems. Many mRNA vaccine

candidates are formulated without any delivery system, indicating the need for further
improvement of mRNA vaccine delivery systems. Currently, lipoplexes and lipid-based

nanoparticles are mainly used to deliver mRNA. Lipid-polymer hybrid nanoparticles offer great

promises in terms of safety, stability, high transfection efficiency and low cost. Continuous

advancement in mRNA formulation and delivery using a variety of nanomaterials could improve

the widespread use of mRNA in the treatment and prevention of disease and cancer.

In conclusion, the twenty-first century is an age of innovation and technological

development. Today, fortunately, there are vaccines that help doctors and scientists save

countless lives. It is true that mRNA vaccines are a big step for immunology and medicine in

general, but as I mentioned before, the process of improving this vaccine comes with several

problems: the vaccine delivery system, its storage and stabilization .After the great efforts of

scientists, most of the problems have been completely or partially solved, but I believe that

over time, technology and people will develop in such a way that mrn vaccine defects will

no longer be a problem and their use will bring great benefits to humanity.
References

1) Garde, Damian. (November 10, 2020). StatNews. The story of mRNA: How a once-

dismissed idea became a leading technology in the COVID vaccine race.

2) Jones K.L., Drane D., Gowans E.J. Long-term storage of DNA-free RNA for use in

vccine studies. BioTechniques. 2007; 43: 675–681.

3) Reichmuth A.M., Oberli M.A., Jaklenec A., Langer R., Blankschtein D. Delivery of

mRNA vaccine using lipid nanoparticles. Ther. Deliv. 2016; 7: 319-334.

4) WHO Coronavirus Dashboard (June 2021). Root analysis (January 2021). mRNA

Therapy and Vaccines Market, 2020-2030.

5) Uddin, Mohammad N., and Monzurul A. Roni. 2021. "Challenges of Storage and

Stability of mRNA-Based COVID-19 Vaccines" Vaccines 9, no. 9: 1033.

https://doi.org/10.3390/vaccines9091033

6) Knezevic, Ivana, Margaret A. Liu, Keith Peden, Tiequn Zhou, and Hye-Na Kang. 2021.

"Development of mRNA Vaccines: Scientific and Regulatory Issues" Vaccines 9, no. 2:

81. https://doi.org/10.3390/vaccines9020081