Covid-19 is an infectious disease that has quickly escalated into a global pandemic. As of January 9, 2021, there are 652,473 reported cases of Covid-19 in Canada and 16,833 deaths. In Ontario, there are a total of 211,837 Covid-19 casesand 4,922 deaths to date. The need to control this escalating situation has led to an acceleration in vaccine development. Currently, 245 vaccine candidates worldwide are in the pipeline for development, 63 of which are now in clinical trials, testing the vaccine on human subjects. In Canada, the approved Pfizer/BioNTech and Moderna vaccines are currently being administered. Like many students and faculty in STEM fields, Professor J. Tim Westwood of UTM’s Biology/Cell and Systems Biology Department has become keen on learning more about these innovative scientific discoveries.
The two mRNA vaccines approved by the FDA and Health Canada, Pfizer/BioNTech and Moderna, are given in two doses. The Pfizer/BioNTech doses are administered 21 days apart, while the Moderna Covid-19 vaccine requires a 28 day interval between the first and second dose. Moreover, developments continue to occur as scientists investigate whether the Moderna vaccine can be administered in one dose with the same efficacy. As of January 9, 103,263 Covid-19 vaccine doses have been administered in Ontario. In addition to the Pfizer/BioNTech and Moderna vaccine, the government of Canada has also purchased vaccines from AstraZeneca, Medicago, Sanofi-GlaxoSmithKline, Novavax, and Johnson & Johnson. In Ontario, initial vaccine roll-out plans involve the vaccination of the at-risk populations, such as residents of long-term care and retirement homes and front-line health care workers. The immunization of the general Ontario population is intended to occur when more doses become readily available.
“A vaccine is any entity that will produce an acquired immune response in a person,” explains Professor Westwood. The vaccine can be manufactured using various approaches. For example, the whole virus itself can be inactivated and presented in the form of the vaccine, inducing an immune response without causing the disease itself. Alternatively, a protein required for the virus to enter the cell can be incorporated into the vaccine. Professor Westwood explains that the protein is grown in laboratory systems and is then presented to the host in the form of a vector. Subsequently, the host, such as a mammalian cell, replicates the protein, which can be glycosylated, and purified to isolate the protein. This protein is then prepared in the form of a vaccine and given to individuals to protect them against the virus. The development of vaccines against Covid-19 involved many diverse approaches to vaccination, some of which have not been commonly used for humans—such as the mRNA and DNA vaccines.
“The [process of vaccine development] was compressed to five to 10 times faster than it would normally happen,” explained Professor Westwood when discussing the difference in the development of the Covid-19 vaccines compared to traditional vaccines, which take multiple years. There was significant pressure to quickly develop the vaccine against Covid-19, which sped up the development steps.
Firstly, the SARS-CoV-2 virus was quickly sequenced, and the variations in its sequence were investigated. The main strategy was to focus on the component of the virus, which attaches to the host cell membrane, causing infection. It was determined that the Spike protein of the virus fuses with the ACE2 (Angiotensin-Converting Enzyme 2) receptor to gain entry into the cell. The presence of the Spike protein was identified due to its similar 3D structure to general models of a typical viruses’ host cell membrane. Therefore, the Spike protein was used in many vaccine approaches and as an antigen, which triggers an immune response.
Professor Westwood explained that the Spike protein sequence was incorporated into a vector in the DNA and mRNA vaccines. The developmental steps were sped up to create vaccine candidates quickly in a situation where a vaccine was imperative. Viable candidates were ready to test by late March or early April. Professor Westwood states how “[the] things that normally [take] several months [were done] in several weeks instead.”
This last year saw a difference in the development and testing of vaccine candidates for Covid-19. Professor Westwood explains that after a vaccine is developed and tested with animal subjects in preclinical trials, clinical trials occur where the vaccine is administered to human individuals. This is called Phase I, which typically takes six months to one year and is conducted to evaluate the toxicity of the candidate. Subsequently, Phase II often takes two years and evaluates the efficacy of the candidate. Similarly, Phase III trials also assess the effectiveness in a larger test group, which takes approximately three years. After the Phase III trials, two years are taken to compile and analyze the data presented and gain approval from the Food and Drug Administration (FDA).
“[The] five-to-six-year process [was] condensed down to five to six months,” says Professor Westwood regarding the testing and approval of the currently approved vaccines against Covid-19. An uncommon event that took place due to the encouragement of the major governments in the scaled-up manufacturing of the vaccines. As opposed to large companies that provide funds to the laboratories under normal circumstances, governments provided funding for this urgent matter.
The Pfizer/BioNTech vaccine is an mRNA vaccine that encodes the Spike Protein in the form of mRNA. The Phase II and Phase III trial results of the vaccine demonstrated 95 per cent efficacy against the virus. With a sample size of 43,448, a total of 170 cases of Covid-19 were recorded in the trial groups—of which eight cases were observed in the experimental group, and 162 cases were recorded in the placebo group. The vaccine was approved by the FDA on December 11, 2020, for emergency use on individuals over the age of 16. Soon after, Health Canada approved the Pfizer/BioNTech vaccine on December 9, 2020, for those over the age of 16.
The Moderna vaccine also employs the Spike protein of the SARS-CoV-2 virus encoded in mRNA encapsulated by lipid-nanoparticle. Phase III trial results demonstrated 94.1% efficacy, a total of 196 cases were reported—185 of which were observed in the placebo group, and 11 cases were recorded in the experimental group. FDA approved the Moderna vaccine on December 18, 2020, for individuals over the age of 18 years. Health Canada approved the Moderna vaccine on December 23, 2020, for individuals aged 18 years or older.
The Pfizer/BioNTech vaccine requires maintenance at a temperature of ‑80ºC to ‑60ºC, whereas the Moderna vaccine can be maintained at a temperature of 2°C to 8°C. When asked about the difference in storage and maintenance conditions of the two vaccines, Professor Westwood explains that the difference has to do with the stabilization approach used by the companies. The approach used by Moderna to stabilize the mRNA allows the vaccine to be stored at a higher temperature than the Pfizer/BioNTech vaccine, which does not stabilize the mRNA to the same extent.
According to Professor Westwood, the biology and STEM community have positively reacted to the rapid approval of the vaccines. The community is optimistic about the newly approved vaccine and satisfied with the high efficacy rates observed in both vaccines. Professor Westwood explains that there was an initial worry about the mRNA vaccine approach used, which usually demonstrates an efficacy rate of 60-70 per cent; hence the 95 per cent and 94.1 per cent efficacy of the vaccines was a source of optimism for the biology and STEM community.
Professor Westwood also stresses the importance of planning follow-ups with those receiving the vaccine to monitor the prevalence of cases in the vaccinated individuals, providing the STEM community with an improved understanding of immunization efficacy against Covid-19. This can be achieved by randomly testing for Covid-19 in communities with a previously high infection rate prior to vaccination.
There exists an apprehension in the community towards the Covid-19 vaccine and vaccines in general as well. Professor Westwood notes that this exists in part due to the lack of understanding and education on vaccination. Conspiracies circulating social media regarding the virus itself and the function of the vaccine have led to the hesitation of the rapidly produced Covid-19 vaccines. Some often believe that one’s condition following vaccination is caused by the vaccine itself when this isn’t always the case. “Correlation is not causation,” says Professor Westwood. Individuals and the media have mistakenly reported a reaction observed after vaccination to be caused by the vaccine itself without concrete evidence.
When a part of the community does not learn what is in a vaccine or how it functions, they are easily engulfed by circulating conspiracies. Professor Westwood believes that if basic knowledge on vaccines is given in high school, it will decrease apprehensions. “It is so important to teach at least some understanding of [vaccines] at a lower level,” says Professor Westwood. By having a minimum knowledge of the vaccine components and how they function, the growing population will be able to make informed decisions about their own health.
The Covid-19 global pandemic puts many lives in danger every day, and the need for proper vaccination is becoming apparent to battle this disease. The rapid development and approval of the Pfizer/BioNTech and Moderna mRNA vaccines have allowed us to move one step closer in the vaccination and protection of the population against the SARS-CoV-2 virus. The emergence of the vaccine has also allowed us to save lives and come one step closer to returning to our life before the pandemic.