Everything You Need to Know About COVID-19 Vaccine Trials Globally

By Jiya Chatterjee

Published in Horace Mann Spectrum Magazine, November, 2020

The term “coronavirus” was once a word rarely used in our vocabulary. Now in 2020, there is rarely a conversation that takes place without mentioning the illness. According to the Johns Hopkins Coronavirus Resource Center, as of late Sept 2020 there are over 29,000,000 reported COVID-19 cases worldwide, with about 6,000,000 in the United States alone. Even with social distancing regulations set in place by governments and institutions alike, the numbers continue to rise at alarming rates all over the globe. Many are wondering when this nightmare will come to an end. Researchers are working around the clock in the race to find an effective vaccine against the coronavirus. The question is – how much progress are they really making?

A team from AstraZeneca in collaboration with Oxford University has been cited as the most promising vaccine trial in recent months. The vaccine is a genetically modified version of a common cold virus named adenovirus. Researchers have added genes to the adenovirus genome that code for the coronavirus spike protein. This spike protein causes human cells to become infected with corona. It is hoped that if the vaccine works, the human immune system will recognize the spike protein and destroy it immediately. It was clear that the vaccine, called ChAdOx1 nCoV-19, was one of the frontrunners when Oxford researchers reported a series of positive results during Phase 1 and Phase 2 of the trial on July 20th, 2020. The team, led by Oxford University researcher Sarah Gilbert, found that many trial patients’ immune systems were responding in a desirable way while also not displaying any harmful side effects. This meant that Phase 3 of the trial could begin. Phase 1 of trials means that the new vaccine is tested on a small group of healthy patients, Phase 2 refers to testing on a slightly larger group of people with more medical diversity, and in Phase 3 testing is performed on hundreds to thousands of patients. During Phase 3, however, the team came across their first bump in the road. On September 6th, 2020, the trial was paused when one of their trial patients suffered serious side effects, possibly from the vaccine, in the form of transverse myelitis, which causes extreme pain and even paralysis due to inflammation along the spinal cord. This created obvious concern, with the National Institutes of Health (NIH) opening an investigation into the case. It was believed that AstraZeneca was not being as transparent about its trials as it could possibly be. Although the trials resumed on September 12th, 2020 after the UK’s Medical Health Regulatory Authority (MHRA) deemed it safe, there are still people calling into question the safety of the AstraZeneca vaccine, such as Marie-Paule Kieney , a researcher at the French national health institute INSERM. “The transparency bar should be set much higher than this latest example” said Kieney to ‘Nature’ in reference to AstraZeneca. Nonetheless, the company has since released a 111-page trial blueprint on September 20th, 2020 that indicated that their vaccine trials were going smoothly again and that their end goal was to have a vaccine that works with at least 50% effectiveness.

Another vaccine that is at a similar stage as the AstraZeneca-Oxford University vaccine is the Pfizer and BioNTech vaccine. This vaccine is unique compared to other vaccines that have been made in the past because this vaccine utilizes messenger ribonucleic acid (mRNA). RNA is used to convert information found in DNA to synthesize proteins needed in the body. mRNA is used to transport the information in DNA outside of the nucleus in order to be translated into protein. The idea behind this vaccine is that the mRNA will teach human cells to make the spike protein, so that over time the body’s immune system will instantly recognize the protein and destroy it. However, while testing seems to be going well for this team, as of September 17th, 2020, experts are saying it is unlikely that this will be the vaccine that will be distributed to the masses. The problem lies in the fact that this vaccine cannot be stored in any freezer warmer than -70°C (-94° F), and almost no freezers in the US can run that temperature. North Carolina has the most locations for ultra-cold freezers in America , and even they have only 10 locations that could potentially be utilized. Vaccines are usually not stored at such low temperatures, and as such, this is a circumstance that has never been addressed before. Nancy Messonnier, director of the Center for Disease Control and Prevention’s (CDC) National Center for Immunization and Respiratory Diseases, says “The complexities of this plan for vaccine storage and handling will have major impact in our ability to efficiently deliver the [Pfizer and BioNTech] vaccine”. However, Pfizer and BioNTech have shown no signs of slowing down, and as of September 12th, 2020 are in the process of expanding the Phase 3 of their trial to 44,000 more participants.

Most research teams have been developing a vaccine that will be an injection, similar to the shots we are all used to taking when we visit the doctor. But who said all vaccines have to be an injection? Imperial College in England has taken a different approach to a coronavirus vaccine; they are in the process of developing an inhalable vaccine. Coronavirus infects humans by either the nose or the mouth, which is why delivering the vaccine through airways may be more beneficial. The university is also developing a regular COVID-19 vaccine alongside a clinical trial of a possible inhalable option. Imperial’s regular vaccine is very similar to that of Pfizer’s vaccine, in the sense that this vaccine uses RNA as well, specifically self-amplifying RNA. Self-amplifying RNA is similar to mRNA, in that it codes for the spike protein, but the rest of the RNA is genetically modified so that the RNA also codes for the antigens that will fight against the virus. It is believed that the self-amplifying RNA vaccine method will produce a better immune response when used on the human body than a vaccine that simply relies on mRNA. Using enzymes, Professor Robin Shattock, head of the Imperial team, recreated the RNA sequence that codes for the spike protein which they are now using in the vaccine. Two vaccines are contestants for the inhalable vaccine; the first one is the AstraZeneca-Oxford University vaccine, and the other one is the self-amplifying RNA based vaccine that Imperial is developing. The two vaccines will be given through a patient's mouth, so that the vaccine will enter straight into the respiratory tract in order to directly target the cells along the airways. The hope is that this method will give a more effective immune response than simply injecting a vaccine into muscle elsewhere in the body.

While there are about 200 coronavirus vaccines being developed around the world currently, there is actually a vaccine that has been released to the public. On August 13th, 2020, President Vladmir Putin of Russia approved the first coronavirus vaccine that would go into circulation. The vaccine, named Sputnik V, is a viral vector vaccine, a method used by Russia in many of the vaccines that they have developed in the past 20 years. A viral vector vaccine uses another virus that the immune system is familiar with to carry the DNA required to code for antigens of the coronavirus into the body so that the immune system will respond. However, there was a lot of skepticism around the approval of Sputnik V. The main reason for concern was the fact that the vaccine was approved before Phase 3 trials could be completed. The approval and distribution was based solely on the fact that results from July show that Sputnik V was given to 76 patients during Phase 1/Phase 2 who all developed antibodies to the coronavirus and showed no side effects. Health officials believe that an appropriate response would have been to continue with testing the vaccine by moving into Phase 3 and gathering more data and results, which is what other researchers have been doing. On September 8th, 2020, the Russian government began distributing the vaccine to civilians. Only time will tell whether this vaccine is all that Russia claims it is to be.

So what does all of this mean? With as many as 24 vaccines being in Phase 3 right now, it seems we are at the final stretch of this pandemic. There is still hope. Science, and researchers have once again proven to be some of the many heroes in the world. What is important though is that governments globally should work together to ensure that the vaccines are delivered to those who are the most vulnerable. On September 22nd, 2020, 156 countries entered into an agreement called COVAX where each nation pledged to help distribute vaccines to a minimum of 3% of all participating countries’ populations (The United States and China will not take part in this agreement). This is progress in the right direction. However, while the end may or may not be in sight, we must continue to follow the guidelines set in place by the most qualified professionals from the CDC who are trying to ensure our safety. That means continuing to wear masks and following proper social distancing rules. The time to get together with friends and celebrate the end of coronavirus has not arrived yet. But hopefully, with all the progress we are seeing globally, we will be able to do that in the not so distant future.

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