An mRNA Vaccine against SARS-CoV-2- Preliminary report.

Jackson, L.A., Anderson, E.J., Rouphael, N.G., Roberts, P.C., Makhene, M., Coler, R.N., McCullough, M.P., Chappell, J.D., Denison, M.R., Stevens, L.J. and Pruijssers, A.J. (2020)

Summarised by Naemi Shahipeni.

An mRNA Vaccine against SARS-CoV-2 — Preliminary Report

Severe acute respiratory syndrome coronavirus virus-2 (SARS-CoV-2), also known as 2019 novel coronavirus (2019-nCoV) was first reported in Wuhan, China in 2019. The virus spread globally, affecting millions of people worldwide. The virus causes COVID-19, a disease affecting the lower respiratory tract with a dry cough, fever, and difficulty in breathing being some of the most common signs, as well as respiratory failure and/or death in severe situations. In addition to morbidities and mortalities, the pandemic has crippled economies and caused widespread panic and anxiety. Unfortunately, there is currently no specific treatment or approved vaccine. This review is about a phase I clinical trial for an mRNA-based SARS-CoV-2 vaccine candidate.

This mRNA-based vaccine is one of its kind: although some companies have vaccine candidates for various infectious diseases and cancer in various stages of vaccine development, there is currently no approved mRNA vaccine for any disease or condition. The mRNA vaccine for SARS-CoV-2 is based on its spike protein, which interacts with the host receptor, ACE2. Viral spike protein mRNA will be coated with a four-lipid nanoparticle, intramuscularly injected into subjects and uptaken by antigen-presenting cells resulting in expression of the viral spike protein by the host and subsequent immune response. Basically, virus spike protein genetic information is injected into subjects and the human body makes/expresses the virus antigen required for an immune response against the virus. This vaccine method offers several advantages over traditional methods in that:

  1. The use of nanoparticles protects the mRNA from degradation and facilitate its uptake by antigen-presenting cells.
  2. The nanoparticle coat also acts as an adjuvant, enhancing the immune response.

The results of this clinical trial showed that two doses are required for the generation of sufficient neutralizing antibodies and that the vaccine candidate is safe with minimal short-term adverse reactions. It elicits production of both binding and neutralizing antibodies that are similar to or greater than antibodies produced from natural infection (a dose-dependent phenomenon) and finally, the vaccine candidate also induces a strong T-help response with subsequent cytokine production such as interferon-gamma, which inhibits virus replication.

In spite of the challenges the vaccine platform has overcome (mentioned above), mRNA vaccines still face concerns of mRNA integration into the human genome which research has addressed: “the vaccine is a transient carrier of mRNA” (Schlake, Thess, Fotin-Mleczek, & Kallen, 2012).

MODERNA’S S-2P mRNA vaccine was developed and produced in two months. The vaccine requires two doses for an effective immune response to occur and resulted in no serious trial-halting adverse effects during this stage of clinical trials. The vaccine candidate has moved on to later clinical trials to test for more immunological responses as well as safety and long-term side effects respectively.

Additional references

• Calina, D., Docea, A. O., Petrakis, D., Egorov, A. M., Ishmukhametov, A. A., Gabibov, A. G., … Tsatsakis, A. (2020, July 1). Towards effective COVID‑19 vaccines: Updates, perspectives and challenges (Review). International Journal of Molecular Medicine, Vol. 46, pp. 3–16. https://doi.org/10.3892/ijmm.2020.4596

• Hamming, I., Timens, W., Bulthuis, M., Lely, A., Navis, G., & van Goor, H. (2004). Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. The Journal of Pathology, 203(2), 631–637. https://doi.org/10.1002/path.1570

• Hofmann, H., & Pöhlmann, S. (2004, October 1). Cellular entry of the SARS coronavirus. Trends in Microbiology, Vol. 12, pp. 466–472. https://doi.org/10.1016/j.tim.2004.08.008

• Khailany, R. A., Safdar, M., & Ozaslan, M. (2020). Genomic characterization of a novel SARS-CoV-2. Gene Reports, 19. https://doi.org/10.1016/j.genrep.2020.100682

• Sawicki, S. G., Sawicki, D. L., & Siddell, S. G. (2007). A Contemporary View of Coronavirus Transcription. Journal of Virology, 81(1), 20–29. https://doi.org/10.1128/jvi.01358-06

• Stadler, K., Masignani, V., Eickmann, M., Becker, S., Abrignani, S., Klenk, H. D., & Rappuoli, R. (2003). SARS — beginning to understand a new virus. Nature Reviews Microbiology, 1(3), 209–218. https://doi.org/10.1038/nrmicro775

• Thiel, V., Ivanov, K. A., Kos Putics, ‘A., Hertzig, T., Schelle, B., Bayer, S., … Ziebuhr, J. (n.d.). Mechanisms and enzymes involved in SARS coronavirus genome expression. https://doi.org/10.1099/vir.0.19424-0

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