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Frontrunners in Vaccine Formation

While there remains a great possibility that developing a vaccine may take as long as several years, we would like to share some updates that will encourage you to develop a much more optimistic outlook on vaccine development in regards to COVID-19. Researchers across the globe are quite hopeful about developing a vaccine based on our progress in this “race to a cure”.


In this article, we will be exploring three main vaccine frontrunners as of May 30, 2020:

  1. Moderna: A pharmaceutical company based in the United States that has been working towards the development of an RNA Vaccinea vaccine containing molecules that are designed to set up a temporary protein factory outside a cell’s nucleus and attach to the cell’s ribosomes. The “factory” translates the mRNA sequence into a protein, which self-destructs in a day. The U.S. Food and Drug Administration (FDA) has consented to Moderna to begin the Phase 2 of their trials, which requires them to perform clinical testing on animals.

  2. Oxford University: Researchers at one of the world’s top universities have been comparing patterns in viral strains from COVID-19 to previous illnesses such as the Middle East Respiratory Syndrome (MERS) and the Severe Acute Respiratory Syndrome (SARS). Similar to Moderna, they have completed the Phase 1 for their vaccine, ChAdOx1 nCoV-19, and are waiting for data to be released. Once they are approved, they will commence further phases.

  3. Pfizer: In collaboration with BioNTech, a German pharmaceutical company, they have been working towards a vaccine called BNT162. Although Phase 1 has not yet begun in the United States, Germany has initiated trials.

Moderna’s RNA Vaccine (mRNA-1273)


Messenger RNA(mRNA) drugs are easier to control than therapy, however, due to the many mRNA therapies that exist, our immune systems view them as large molecules that attack cells, similar to viruses. Although in most cases our immune systems launches its defence system to destroy the mRNA, mRNA-1273 is designated to direct cells to make a protein that can work as a drug or a vaccine. The mRNA does this by entering the cell, avoiding destruction by the immune system, and then being translated later on. 


First, the vaccine is injected into cells as a lipid nanoparticle that contains the mRNA strand. The instructions for the creation of the spike protein, an important component discovered prior to the virus, is carried within the mRNA strand, which is why a heavy emphasis is placed on the viability of the strand making it past the immune system. The cells in our body recognize chemical markers in the mRNA, preventing the immune system from destroying the strand. Finally, as the strand infiltrates the body, the mRNA begins the process of creating specialized proteins that will target the virus. 


As mentioned earlier, the company received the FDA on May 12. Additionally, they announced positive interim Phase 1 data for the vaccine and the Investigation for a New Drug (IND) was submitted by the company on April 27 for Phase 2 of clinical trials.



A video explaining the mRNA-1273 vaccine, extracted from Moderna's website.


Oxford University’s Vaccine(ChADOx1nCov-19)


ChADOx1nCov-19 originates from a weakened version of adenovirus(the common cold virus) that causes infections in chimpanzees. Over time, the adenovirus has evolved so that it is impossible to thrive in humans.


The virus has been genetically modified by researchers. Genetic material has been added to the ChADOx1 structure, which also happens to be the building block for making proteins in the COVID-19, called Spike glycoprotein. This protein is found on the surface of COVID-19 and plays an important role in its method of infecting individuals. COVID-19 uses this spike protein to bind to receptors on human cells to gain entry and cause an infection.


This vaccine allows the body to recognize and develop an immune response to the spike protein so that the body can defend against COVID-19. Oxford’s researchers have made great progress considering that they began their research in February of 2020, and managed to get the vaccine approved a month after. Upon launching the first phase of human trials in April, they are yet to begin the second and third phase.


A video from the University of Oxford; The launch of human trials marks an important milestone in their vaccine ChADOx1nCov-19's development .


Pfizer X BioNTech’s Vaccine (BNT162)


Three companies: Pfizer, Fosun, and BioNTech, in collaboration, have given their four vaccines the general name of BNT162. However, each variation of the vaccines: BNT162a1, BNT162b1, BNT162b2, and BNT162c2M represent a different combination of mRNA and target antigen.

  • Two of the vaccines involve modRNA, which is nucleoside modified mRNA. Nucleotides are similar to nucleosides, however, nucleosides lack a phosphate in their makeup. Nucleosides are composed of a molecule of sugar linked to compounds called nitrogenous bases (adenine, guanine, cytosine, thymine, or uracilonly found in RNA). Nucleosides and nucleotides are the structural subunits of nucleic acids. These vaccines synthetically change the nucleosides of COVID-19’s mRNA so that it is less lethal and able to withstand the human body without degradation. 

  • One of the vaccines involves a uridine containing mRNA (uRNA). Uridine is a derivative of the nitrogenous base uracil. This variation of an mRNA vaccine is currently in testing stages.

  • The last vaccine contains a self-amplifying mRNA (saRNA). SaRNA is a type of messenger RNA that uses a duplicate of its strand to produce an opposite effect in the body. In this case, the idea behind using saRNA in the vaccine would be to build an immunity of sorts in the body against COVID-19. 


Bottles with labels: Vaccine COVID-19(Reuters)


Similar to mRNA-1273, each of the vaccine candidates is encased in a lipid nanoparticle to inject into patients. Two of the vaccines have sequences that code for large spike proteins, while the other two sequence for smaller spike proteins. Dosing in the United States has commenced this week, however, Phase 3 will be approved soon after data from the first and second phase has been released.


Conclusion: These are just three of the many vaccines that scientists from all across the world are working towards. As we wait for these companies to proceed with further phases in vaccine formation, we must also remember to study the new trends that are coming up upon analyzing new data. Although we are still unaware of an exact launch date of the vaccine for COVID-19, we are certain that our researchers are setting a new standard for future research during these unprecedented times.


References:

Chauhan, Y. (2014, April 17). Nucleoside. Retrieved May 25, 2020, from

https://www.britannica.com/science/nucleoside

GEN Staff. (2020, May 18). BioNTech, Pfizer, and Fosun Pharma – BNT162. Retrieved May 25, 2020, from

https://www.genengnews.com/covid-19-candidates/biontech-pfizer-and-fosun-pharma-bnt162/

Moderna. (2020, May 19). Moderna’s Work on a COVID-19 Vaccine Candidate.

Retrieved May 25, 2020, from

https://www.modernatx.com/modernas-work-potential-vaccine-against-covid-19

Rees, V. (2020, May 6). First patient dosed with Pfizer’s potential COVID-19 vaccine in US. Retrieved May 25, 2020, from

https://www.europeanpharmaceuticalreview.com/news/118993/first-patient-dosed-with-pfizers-potential-covid-19-vaccine-in-us/

Servick, K. (2020, May 25.). Meet the company that has just begun testing a coronavirus vaccine in the United States. Retrieved May 25, 2020, from

https://www.sciencemag.org/news/2017/02/mysterious-2-billion-biotech-revealing-secrets-behind-its-new-drugs-and-vaccines

University of Oxford. (2020, April 23). Oxford COVID-19 vaccine begins human trial stage. Retrieved May 25, 2020, from

http://www.ox.ac.uk/news/2020-04-23-oxford-covid-19-vaccine-begins-human-trial- stage

Worrachate, A. (2020, May 24). Oxford University vaccine trials run into hurdle: Telegraph. Retrieved May 25, 2020, from

https://www.bnnbloomberg.ca/oxford-university-vaccine-trials-run-into-hurdle-telegraph-1.144053

Featured image courtesy of Wix.


Article Researcher: Rahma Osman

Article Contributer: Palak Agarwal