Written By: Isaiah Hazelwood and Omar As’sadiq

What Are Vaccines and How Do They Work?

The human immune system works to provide long-term immunity against diseases that enter the body. One of the methods it does so is by producing antibodies from T-Cells that bind to antigens of a pathogen and destroy it. In addition, most immune reactions produce memory cells during the first infection that helps release antibodies fast during a secondary infection. In a sense, our own bodies are capable of producing antibodies and memory cells that prevent us from getting sick when we get infected a second time by the same pathogen. So why do we need vaccines in the first place?

Vaccines are used to provide natural active immunity without getting sick in the first place. They are especially necessary when a deadly virus like COVID-19 causes severe lethal symptoms which the human immunity system is not efficient enough to fight. Vaccine development has changed dramatically throughout the year. In the past, vaccines were made by creating a weakened version of a pathogen, such as a virus, and injecting it into our body such that our immune system could detect the protein antigens in the weakened virus and make antibodies without the virus causing any severe symptoms, however, those types of vaccines usually take years and years of research and perfection. Nowadays, with innovative technologies, new developments like mRNA vaccines can be produced much faster with more effective results. 

Why are there new vaccines for the flu each year and what does that mean for COVID?

Vaccines provide long term active immunity by allowing our immune system to be triggered against a certain weakened/unharmful pathogen by producing antibody proteins with a specific shape that binds to the complementary shape of the pathogen protein destroying it, leading to production of memory cells. If vaccines are meant to provide long-term active immunity against a specific pathogen-causing disease that could last for years, why are we required to take new flu vaccines each year? The simple answer is mutations. What a lot of people do not know is that mutations are inevitable, and they occur every day due to factors such as radiation causing alterations in the DNA or RNA of organisms and pathogens. Flu viruses mutate very quickly each year into new strains, and if genetic material codes for proteins, then altered genetic material in flu viruses would cause the production of different proteins that have different shapes to the antibodies produced from previous vaccinations.

Luckily, our wide databases, developments, and research on flu vaccines have helped us to identify mutant strains and develop new flu vaccines each year. But what does this mean for COVID? Will we have to develop a new vaccine each year? We are not sure yet. The scientific community needs to assess the viral mutation rate of the COVID vaccine and the effectiveness of the current vaccines against possible future strains in order to determine if a new vaccine needs to be developed. 

What is herd immunity and how will COVID-19 vaccines help achieve that?

Mayo Clinic defines herd immunity as the process where a large portion of a community (the herd) becomes immune to a disease, making the spread of disease from person to person unlikely. As a result, the whole community becomes protected — not just those who are immune.

To put it in simple words, when a certain proportion of the population is immune, called the threshold proportion, those who are immune will not get symptoms and infect others while those who are not immune will most likely not get the disease because the majority of the population is immune. It is at that point when herd immunity is achieved that a pandemic could be declared officially controlled.

Herd immunity could be achieved either by natural immunity, where most of the population gets the disease, develops symptoms, and then gains immunity, or by the process of vaccinations. Both methods depend on the production of active immunity by the human body. The exact threshold proportion needed to achieve herd immunity varies from 70-90%, but scientists estimate 70% is needed to halt the COVID-19 pandemic.

Main upcoming COVID vaccines and how they work

Pfizer, an American company, and BioNTech, a German company, were the first to announce a successful COVID vaccine candidate on November 9. The Phase 3 clinical trial for their vaccine candidate began on July 23 and recruited 43,538 participants. Their initial November 9th announcement, based on the trial’s preliminary data, gave the vaccine a 90% success rate, and they released the trial’s final results on November 18th which gave the vaccine a 95% success rate. Their vaccine, which is given as two injections several weeks apart, is based on viral mRNA which codes for a non-damaging COVID-19 protein (specifically, the “Spike” protein on the virus’s surface). When the vaccine is injected, the body creates a small amount of viral protein before degrading the mRNA; the immune system detects this viral protein, raises an immune response, and prepares itself for a future appearance of the protein. As the first vaccine candidate, it is rapidly being considered by governments and has already been approved by the UK, Health Canada, and the U.S. Food and Drug Administration. Even when approved, the vaccine will likely face obstacles in mass manufacture and transport, as the mRNA in the vaccine must be kept below -70℃ at all times. 

Quickly after Pfizer announced preliminary vaccine results on November 9, the U.S. company Moderna followed suit by releasing preliminary data on their vaccine candidate on November 16. The Moderna clinical trial, which involved 30,000 participants, began on July 27 and gave a preliminary effectiveness of 94% – on par with Pfizer’s results. Moderna’s vaccine candidate is a mRNA vaccine with a near-identical mechanism to Pfizer’s candidate, but it is much more stable and can be stored at -20℃. The US is currently reviewing Moderna’s candidate for emergency approval.

AstraZeneca, a British company, collaborated with Oxford University to develop a vaccine candidate based on a non-replicating virus modified with COVID surface proteins which triggers an immune response against the COVID proteins on the non-dangerous non-infectious virus in the injection. AstraZeneca’s vaccine candidate began a 30,000-person clinical trial on August 31 across Brazil and the United Kingdom. The trial was briefly paused in September after one subject experienced spinal cord inflammation, but this event was tied to external events rather than the vaccine and the trial resumed. The trial’s preliminary data released November 23 found its effectiveness ranged between 62% and 90% based on the dose with an average of 70% effectiveness; unusually, the higher-dose group received less effective protection than the lower-dose group, which was unexpected but possible given the complexities of the immune system. Given these complications, some researchers call for the clinical trial’s repetition to confirm the vaccine’s effectiveness. While this effectiveness is lower than that of Pfizer and Moderna’s candidate vaccines, it still exceeds the 50% effectiveness expected by regulators. In addition, AstraZeneca’s virus-based vaccine is much easier to transport than its competitors, requiring normal refrigeration at 2℃ rather than the extreme cold of mRNA-based vaccines.

Within the United States, two other major vaccine candidates are currently being tested by the companies Noravax and Janssen. The Noravax candidate uses a molecule based on the COVID-19 spike protein to build an immune response while the Janssen candidate uses a non-replicating viral vector similar to AstraZeneca’s vaccine. These vaccines are both undergoing Stage 3 clinical trials, but no preliminary data has currently been released on their effectiveness – though we can expect to see more information soon.  

Outside of the United States and Europe, four main vaccines candidates proposed by four groups are undergoing Phase 3 clinical trials: the Chinese company Sinovac and the state-owned Chinese company Sinpharms are testing two candidates based on COVID-19 modified to be safe and non-infectious while the Chinese company CanSino and the Russian Gamaleya Research Institute of Epidemiology and Microbiology, alongside the Russian government, are testing two candidates based on non-infectious viruses modified to express COVID-19 proteins. While these vaccines candidates are still in development, they are expected to cost less and be easier to transport than American and European alternatives.

Despite the lack of reviewed evidence on these vaccines, possibility of reduced effectiveness or side effects, and the lack of transparency in their clinical trials, China and Russia are rushing to begin use of these vaccines. Russia’s vaccine, stated to be 90% effective, had an extremely small sample size of 76 people in its Phase 1 and 2 clinical trials and the government has begun its production and rollout before the conclusion of Phase 3 clinical trials. The Chinese government has given emergency approval to the Sinovac and Sinopharm vaccines, despite incomplete clinical trials, and has already administered them to approximately 1 million people. Their widespread early use has raised concerns that China and Russia are using their vaccines as political tools rather than as medical treatments.

The Canadian government is preparing to authorize and implement vaccines as soon as they can be proved safe and effective. The Pfizer vaccine was the first to receive approval on December 9, and Health Canada has been considering vaccine applications from AstraZeneca, Moderna, and Janssen since September and will likely approve them once the full results of their clinical trials are completed. The Government of Canada has also negotiated agreements to purchase a combined 410 million vaccine doses from Pfizer, Moderna, AstaZeneca, Janssen, Noravax, Medicago, Sanof, and GlaxoSmithKline once the vaccines are approved.

How long will immunity from vaccines last?

While infection by a virus generally gives the immune system lasting protection against the virus in the future, there have been rare cases of reported reinfection by SARS-CoV-2. Due to the extremely small number of cases of reinfection, with roughly a dozen reported among tens of millions of infections, little information on the reasons for reinfection is available: while the reinfection could be caused by a mutated SARS-CoV-2 virus which bypasses the first immune response, the reinfection could also be caused by a rare abnormally weak immune response to the first infection which is insufficient to provide future immunity. Until more cases of reinfection appear, or a study can be performed to examine reinfection, the length of immunity given by infection is unknown.

Each vaccine candidate has a different mechanism for generating an immune response, and each vaccine candidate will create a different level of immune response. To assist in providing immunity, many vaccine candidates including Pfizer’s, AstraZeneca’s, Moderna’s, and Noravax’s are given in two spaced doses to generate two immune responses that provide stronger immunity. Currently, little information is available on the exact length of time each vaccine provides immunity, as clinical trials and human use began relatively recently. Moderna’s preliminary results included data showing their vaccine continues to generate an immune response to SARS-CoV-2 three months following infection, but immunity past this time is unconfirmed – though likely.

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