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In late 2019, a novel coronavirus (SARS-CoV-2) took the world by storm. Cases of this enigmatic and never-before-seen strain of virus spread through country after country just after the New Year, and the rest is history. In January 2020, the SARS-CoV-2 virus spread to Canadian shores. It challenged medical professionals and scientists as they gathered data regarding the symptoms of those infected and the best way to detect the virus, while each provincial government frantically began closing all non-essential services to prevent chains of transmission. It did not take long before several research teams began working on a potential vaccine, but many questions may arise regarding the science directly related to these vaccines - not to mention their safety and efficacy.
The Process
Dr. Halperin, a professor of Pediatrics and Microbiology and Immunology at Dalhousie University, says that the process for developing a vaccine can be divided into two stages: the preclinical work in the laboratory setting, and the actual clinical trials. The preclinical work involves research to understand the pathogen, discover how it causes disease, and characterize the body’s natural immune response to the pathogen. Next, the researchers attempt to create a vaccine that inhibits the specific binding receptor on the surface of the virus to prevent it from invading cells. Once a potential vaccine is developed, it is screened “to determine the toxicity to animals under certain conditions and assess the safety of that vaccine,” before it would be eligible to continue to the clinical setting.
Dr. Halperin describes the first phase of clinical trials as one where “the safety and tolerability of the vaccine will be tested first in younger adults, and then in older adults.” The clinical trials consist of three “phases” before a vaccine can be made available on the market. The first and second phases consist of small and large numbers of test subjects where any adverse events are identified, along with any potential differences in immune responses from the preclinical work to human trials. These phases are arguably the most important, as the human immune response to the vaccine presents itself and is analyzed in detail. Any differences in the activity of T-cell responses, cellular immunity, and antibody levels in the blood, which are all aspects of an immune response, are recorded and analyzed. Phase three trials are intended to confirm and expand on safety, effectiveness, and efficacy results from phase 1 and 2 trials of the vaccine, and to evaluate the overall risks and benefits of the drug being studied.
Understanding our Body’s Response
As we move into this section, it is important to note that there are two prominent and distinct types of vaccines in use to fight against SARS-CoV-2: mRNA vaccines and vector-based vaccines. Essentially, mRNA vaccines contain genetically engineered mRNA from SARS-CoV-2 (the virus that causes COVID-19 infection) and encodes instructions for our cells to generate a harmless CoV-2 protein called the spike protein [2]. Once our cells begin synthesizing this protein, we form T- and B-lymphocytes to initiate an immune response that will recognize the spike protein in future exposures [2]. The presence of these lymphocytes, along with the capability to produce specific antibodies, can help fight infection from SARS-CoV-2 [10], [2]. Two examples of mRNA vaccines currently in use are those produced by Pfizer-BioNTech and Moderna.
On the other hand, viral-vector vaccines involve an attenuated version of an adenovirus into which genetic material from COVID-19 is inserted [2]. This genetic material then instructs the human cells to synthesize spike proteins, as with the case of mRNA-based vaccines. Similar to mRNA vaccines, the T- and B-lymphocytes then launch an immune response that inactivates the spike protein during future infections. Two examples of vector-based vaccines are those produced by AstraZeneca and Johnson & Johnson.
Vaccines are generally harmless materials aimed to mimic disease-causing agents and stimulate the immune system to build a response against a pathogen. Pathogens are studded with antigens that trigger immune responses when detected by our cells. When vaccination occurs, it is exposing our body to antigens that are similar to those found on the SARS-CoV-2 virus. Due to this exposure, our body is able to build protection against this “pathogen imposter,” by forming a primary response mechanism so that when we encounter the same pathogen in a real-life situation, our body can fight the pathogen more swiftly and effectively [2].
The Pfizer-BioNTech COVID-19 vaccine is manufactured by the Pfizer ULC and BioNTech Manufacturing GmbH [10]. Health Canada authorized this vaccine to begin public distribution on December 9th, 2020 under the Interim Order [13]. Based on the empirical evidence suggested from clinical trials under the CDC, the Pfizer vaccine has a 95% efficacy rate in preventing the laboratory-confirmed COVID-19 illness of those aged 16 or older, and 100% in those aged 12-15 [13].
To understand how this vaccine functions in particular, it is important to understand that the SARS-CoV-2 virus is studded with proteins along its surface that it uses to enter human cells. These spike proteins are what permits scientists to create potential vaccines and treatments related to the virus [5]. The mRNA used to make the vaccine is an extremely fragile and short lasting molecule at room temperature. To protect this molecule from degrading so quickly and to aid its entry into human cells, Pfizer encapsulated it in an oily shell composed of lipid nanoparticles and required the storage temperature of their vaccine to be -70 degrees Celsius [5].
The Pfizer-BioNTech vaccine requires two separate injections separated by a period up to 16 weeks apart, as advised by the National Advisory Committee on Immunization (NACI) [8]. The first dose of the vaccine allows our body to formulate a response against SARS-CoV-2, while the second dose further boosts the immune response to ensure long-term protection [5].
The Moderna vaccine was produced by a Massachusetts-based company that partnered with the National Institutes of Health. Health Canada approved this vaccine under the Interim Order on December 23rd, 2020 [3]. Based on the empirical evidence suggested from clinical trials under the CDC, the Moderna vaccine has a 94.1% efficacy rate in preventing the laboratory-confirmed COVID-19 illness [12].
Similar to the Pfizer vaccine, the Moderna vaccine also utilizes mRNA inside of an oil shell composed of lipid nanoparticles to protect the genetic material, aid in uptake by cells, and act as an adjuvant. Unlike the Pfizer vaccine, the Moderna vaccine does not require specialized refrigerated conditions. Moderna’s vaccine only requires storage at -20 degrees Celsius because of the properties and structure of the mRNA that is used in the vaccine [16]. The Moderna vaccine requires two injections separated by a period up to 16 weeks. These days are used by our bodies to build its protection against the virus [3].
The AstraZeneca vaccine was developed by the University of Oxford and the British-Swedish company named AstraZeneca. This vaccine was authorized by Health Canada on February 26th, 2021 under the Interim Order [12] and has an efficacy rate that can provide protection up to 82% [6]. This vaccine is particularly easy to store in comparison to the others, as it can be stored at 2-8 oC for up to 6 months [4].
Unlike the Pfizer and Moderna vaccines, the AstraZeneca vaccine utilizes DNA as opposed to RNA. Researchers developed a viral vector (an adenovirus) to deliver the genetic information to our cells [11]. The vector was genetically engineered to contain the necessary information to produce SARS-CoV-2 spike proteins, the same protein found on the surface of a virus particle. The vectors containing the information are taken up by our cells, injecting the information to produce the proteins. Fragments of the spike protein are then presented on the outside surface of the cell and are recognized by our immune system to initiate a response and build protection.
Canada then began offering this vaccine to those 55+ in the country, following the guidance of NACI [9]. New Brunswick’s reasoning for continuing to administer this vaccine serves to protect those who are older and are at increased risk for complications from the disease, and determined that the risk of developing severe complications from the disease outweighed the risk of complications from the vaccine according to the most recent data [7].
The difference between the normal development of vaccines and most COVID-19 vaccine studies is that the process will have a significantly compressed timeline. This compressed timeline was ultimately a result of the global collaboration, states of emergency, sufficient resources, and funding being offered by numerous organizations and individuals. Even given the imminent need for the vaccine, researchers were still given the appropriate amount of time to assess the safety, quality, and efficacy of each vaccine along the three phase checkpoints as per usual. According to the Government of Canada, any vaccine must be rigorously tested several times before its usage is approved. Under normal circumstances, it could take up to 10 years of research and development before Health Canada sees fit to approve the vaccine [15]. Sometimes vaccine approval doesn’t take as long and it depends on a lot of factors, including increased funding. Global advancements and new technologies allow for the faster production of new vaccines, but when paired with considerable funding, can speed up this process (as in the situation with the COVID-19 pandemic).
There are many who would question the safety and effectiveness of vaccines produced under a compressed timeline. Health Canada did implement a fast-tracked review process to assess the COVID-19 vaccines, but by no means lowered their standards. Their decisions were based on thorough reviews of all vaccine data produced by each affiliated company and must meet all manufacturing standards where the benefits greatly outweigh the risks [15].
For reference, as of September 3rd, 2021, the Government of Canada released in a status report regarding the vaccine safety that 27.8 in 100,000 doses have reported an adverse event, where 7.5 in 100,000 were considered serious [14]. These adverse events can be defined as an unpredicted medical occurrence following immunization. The occurrence of these events may not be directly related to the vaccine, and there may be confounding variables that influenced the health of the patient with unfortunate timing.
It is also worth mentioning that researchers have been developing mRNA vaccines well before the pandemic. The very first article detailing gene-based therapeutics to produce proteins needed to fight disease was published in 1990 by Wolff et al. Their team inserted gene mRNAs into mice where protein production was successfully detected. The paper can be found here.
The most important action for figures of authority right now is to ensure the clarity of new information as it comes in, and to clarify what is known and not known. This way, trust may be built up in the general public. Engaging in thoughtful discussions about the benefits and risks of getting a COVID-19 vaccine is essential. Amidst all of the misinformation, there is good news. Vaccinations are well underway and there may finally be a light at the end of the tunnel.
Healthcare workers, researchers, the government, and public health agencies must continue what they are doing without compromising the trust of the general public and to continue advocating for better illness protection in a generic sense (i.e. hand washing/ sanitization, communicating the importance of getting vaccinated and where to find reliable and credible resources for learning about new research developments). Advocating for the learning of proper preventative measures will not only aid in keeping oneself as protected as possible against COVID-19, but protected against other viruses and illnesses in the future. It is also extremely important to present new information and developments in a clear and concise manner. This is definitely easier said than done as many aspects of the pandemic are constantly evolving and changing.
Finally, the general public has to continue to have faith in our scientific leaders within our communities as they have everyone’s best interest in mind. The health and safety of the public has and will continue to be at the forefront of all decisions for the rest of this pandemic and officials are working tirelessly and diligently to provide the most accurate and up-to-date information as it becomes available. Be cautious about the spread of misinformation and become familiar with the signs of fake news articles and postings. We all need to work together to protect the vulnerable and all have a part to play in the safe reopening and recovery.
References
[1] Auld, A. (2020, May 19). Researchers at Dalhousie to lead clinical trials of COVID‑19 vaccine. Retrieved January 10, 2021, from https://www.dal.ca/news/2020/05/19/researchers-at-dalhousie-to-lead-human-trials-of-covid-19-vaccin.html
[2] Centers for Disease Control and Prevention. (2020, December 18). Understanding How COVID-19 Vaccines Work. Retrieved January 10, 2021, from https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/how-they-work.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fcoronavirus%2F2019-ncov%2Fvaccines%2Fabout-vaccines%2Fhow-they-work.html
[3] Corum, J., & Zimmer, C. (2020, December 05). How Moderna's Vaccine Works. Retrieved January 10, 2021, from https://www.nytimes.com/interactive/2020/health/moderna-covid-19-vaccine.html
[4] Corum, J., & Zimmer, C. (2020, December 05). How the Oxford-AstraZeneca COVID-19 Vaccine Works. Retrieved January 10, 2021, from https://www.nytimes.com/interactive/2020/health/oxford-astrazeneca-covid-19-vaccine.html
[5] Corum, J., & Zimmer, C. (2020, December 05). How the Pfizer-BioNTech Vaccine Works. Retrieved January 10, 2021, from https://www.nytimes.com/interactive/2020/health/pfizer-biontech-covid-19-vaccine.html
[6] COVID-19 vaccine AstraZeneca confirms 100% protection against Severe disease, hospitalisation and death in the primary analysis of Phase III trials. AstraZeneca. (2021, February 3). Retrieved September 15, 2021, from https://www.astrazeneca.com/media-centre/press-releases/2021/covid-19-vaccine-astrazeneca-confirms-protection-against-severe-disease-hospitalisation-and-death-in-the-primary-analysis-of-phase-iii-trials.html.
[7] Government of New Brunswick, C. (2017, April 24). New Brunswick patient dies with rare blood clot. Retrieved September 15, 2021, from https://www2.gnb.ca/content/gnb/en/news/news_release.2021.05.0350.html.
[8] Government of New Brunswick, Canada (2021, August 24). Pfizer-BioNTech COVID-19 vaccine. Government of New Brunswick, Canada. Retrieved September 15, 2021, from https://www2.gnb.ca/content/gnb/en/corporate/promo/covid-19/nb-vaccine/get-the-facts/pfizer-biontech-covid-19-vaccine.html.
[9] Government of New Brunswick, Canada (2021, August 5). AstraZeneca COVID-19 vaccine. Retrieved September 15, 2021, from https://www2.gnb.ca/content/gnb/en/corporate/promo/covid-19/nb-vaccine/get-the-facts/astrazeneca-covid-19-vaccine.html.
[10] Health Canada. (2020, December 11). About COVID-19 mRNA vaccines. Government of Canada. Retrieved January 10, 2021, from https://www.canada.ca/en/health-canada/services/drugs-health-products/covid19-industry/drugs-vaccines-treatments/vaccines/type-mrna.html#a1
[11] Health Canada (2021, August 27). AstraZeneca / COVISHIELD COVID-19 vaccine. Government of Canada. Retrieved September 15, 2021, from https://www.canada.ca/en/health-canada/services/drugs-health-products/covid19-industry/drugs-vaccines-treatments/vaccines/astrazeneca.html#a2.
[12] Health Canada (2021, January 8). Moderna COVID-19 Vaccine. Canada.ca. Retrieved September 15, 2021, from https://www.canada.ca/en/health-canada/services/drugs-health-products/covid19-industry/drugs-vaccines-treatments/vaccines/moderna.html.
[13] Health Canada. (2021, January 08). Pfizer-BioNTech COVID-19 vaccine. Government of Canada. Retrieved January 10, 2021, from https://www.canada.ca/en/health-canada/services/drugs-health-products/covid19-industry/drugs-vaccines-treatments/vaccines/pfizer-biontech.html
[14] Public Health Agency of Canada (2021, August 12). Covid-19 Vaccine Safety: Weekly Report on side effects following immunization. Canada.ca. Retrieved September 15, 2021, from https://health-infobase.canada.ca/covid-19/vaccine-safety/#a3.
[15] Public Health Agency of Canada. (2020, December 16). Government of Canada. Retrieved January 10, 2021, from https://www.canada.ca/en/public-health/services/diseases/2019-novel-coronavirus-infection/prevention-risks/covid-19-vaccine-treatment.html
[16] Simmons-Duffin, S. (2020, November 17). Why Does Pfizer's COVID-19 Vaccine Need To Be Kept Colder Than Antarctica? Retrieved January 10, 2021, from https://www.npr.org/sections/health-shots/2020/11/17/935563377/why-does-pfizers-covid-19-vaccine-need-to-be-kept-colder-than-antarctica
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