Introduction

The COVID-19 pandemic has led to expedited approvals for the use of messenger ribonucleic acid (mRNA) technology in the development of vaccines. More specifically, it resulted in the first 2 FDA-approved mRNA vaccines commercially distributed by the end of 2020.^1,2

Prior to these vaccines being available, the virus caused more than 1.7 million deaths and almost 72 million confirmed cases worldwide.³ What resulted afterwards was one of the biggest vaccination campaigns in history, with more than 13.1 billion COVID-19 vaccine doses administered worldwide as of January 2023.³

More than 667 million doses have been administered in the United States,⁴ with recent data estimating that these vaccinations have prevented 18.5 million additional hospitalizations and 3.2 million additional deaths throughout the country.⁵ Due to the success of mRNA technology with COVID-19, there has been a significant increase in research looking into utilizing mRNA technology, and more specifically, how it can help to advance vaccine development.

mRNA Technology

Although the first mRNA-based COVID-19 vaccine was authorized for emergency use in late 2020,¹ this technology has been around since the 1970s.⁶ Since then, its use in vaccine production has been a trailblazer in the fight against infectious diseases.

These vaccines use a small piece of genetic material called mRNA to instruct cells to create spike proteins.⁷ Spike proteins are harmless components that trigger the production of antibodies, which is what can reduce a person’s symptoms if they are exposed to the COVID-19 virus.⁷ These vaccines do not utilize a live virus, and their ability to create an immune response to protect the body has been significant with an efficacy rate of more than 94% for both of the commercially available primary series vaccines in the United States.⁸

An important and recent advancement in the production of mRNA vaccines is the manufacturing process called lipid nanoparticle (LNP) technology, which is a more recent development in mRNA use.⁹ LNPs facilitate the delivery of mRNA to cells by encapsulating the mRNA by lipids, and the technology can deliver mRNA in a targeted manner.⁹

Because this technology does not utilize viral components, production of mRNA vaccines can be accomplished at a faster rate than traditional vaccines.¹⁰ Another benefit of mRNA technology is that it can be used to create vaccines for viruses that may otherwise be slow or difficult to grow and identify in the laboratory.¹¹ As seen in Table 1, the benefits of mRNA technology have led to the development of vaccines beyond COVID-19.^12-23

Table 1. Current mRNA Vaccines in the Pipeline

Clinical Evidence for mRNA Vaccines

Research into mRNA technology for vaccines has advanced notably, with multiple vaccines in the midst of phase 3 trials. An mRNA cytomegalovirus (CMV) vaccine is moving into phase 3 after phase 2 data showed that in participants who were seronegative for CMV, their neutralizing antibody geometric mean titers (GMT) against epithelial cell infection were at least 20-fold higher after a third vaccination at baseline.²⁴

Moderna’s mRNA influenza vaccine is fully enrolled in phase 2 and has begun their phase 3 trial.²⁵ Previous data showed that the vaccine increased GMTs against H1N1 and H3N2 strains, and no significant safety findings were observed through day 29.²⁵ More recently, data from the phase 3 mRNA RSV vaccine trial demonstrated vaccine efficacy of 83.7% against RSV, and there are intentions for it to be submitted for regulatory approval this year.²⁶

Other vaccines have showed promising results that are now in phase 1 and 2 trials as well. Findings from a phase 2 trial in which mRNA-4157/V940 was used in combination with pembrolizumab showed that the risk of recurrence or death of melanoma was reduced by 44%, which is a milestone for the vaccine created in collaboration between Moderna and Merck.²⁷

Vaccines starting phase 1 trials have produced data showing strong immune responses in preclinical animal studies, such as the mRNA EBV vaccine that demonstrated levels of antibodies that were higher than those observed in naturally-infected human sera.²⁸ These key developments have sparked interest in the creation of mRNA vaccines for other infectious diseases as well, such as the current preclinical research being investigated for malaria that is being funded by the National Institutes of Health.²²

Limitations of mRNA Vaccines

Although there is a significant amount of research looking into utilizing mRNA for vaccines, it is important to note that there are some limitations to its use. For example, the approved COVID-19 vaccines can be stored for several months depending on the formulation, but only at extremely low temperatures below freezing, which can lead to logistical barriers for distribution in certain areas.²⁹

Furthermore, the need for multiple doses of the mRNA vaccines may pose a challenge for people to complete the series of their immunizations, such as the currently researched PCV vaccine.³⁰ There is also ongoing research looking into the duration of these vaccines, as the development of mRNA vaccines is still in early stages compared to other vaccines and more research is needed before they can widely be used for additional viral diseases.

Conclusions

Despite these limitations, mRNA technology has proven to be a beneficial, efficient, and time saving process in the development of vaccines. Because they can they be tailored to target specific strains of viruses,⁹ mRNA vaccines have the potential to be created in a way that would make them more effective than traditional vaccines, which could change the processes in place when responding to infectious outbreaks.

It is essential that there is continued research and development in this field to ensure that humanity has the resources necessary to combat infectious outbreaks in the future. Additionally, is critical that pharmacists stay informed about the newest advancements in mRNA technology and support endeavors to expand and increase vaccine access.

The past few years of research has resulted in data showing efficacy in mRNA vaccines, likely meaning that mRNA technology is expected to be present in the production of vaccines against other infectious diseases in the future.

About the Author

Paulida Tes, PharmD candidate 2023, Philadelphia College of Pharmacy at Saint Joseph’s University.

References

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