Vaccines were created to elicit an immune response to a disease-producing pathogen. We typically know them as containing either pieces of – or a weakened or dead form of – the pathogen itself, but this has changed in recent years. The initial round of approved COVID-19 vaccines from Pfizer-BioNTech and Moderna represents a new class of vaccines, called mRNA vaccines. These vaccines contain no element of the original pathogen itself, only blueprints, which allows the body to prepare itself for the event of exposure. Whether skeptic, believer, or somewhere between, when the COVID-19 vaccine arrives in your community, you will have an important choice to make that could affect your health and lifestyle.
A brief history
English physician Edward Jenner is credited with creating and administering the first vaccine in 1796. In an experiment intended to find a way to prevent the proliferation of smallpox, Jenner was said to have extracted fluid from the hand of a milkmaid infected with cowpox (a less serious illness linked to smallpox) and injected it into an 8-year-old boy. Six weeks later he exposed the same boy to smallpox and the child did not develop any symptoms. He coined the term “vaccination”, deriving it from “vacca”, the Latin word for cow. By 1980, smallpox was eradicated. Fast-forward 225 years and we have more vaccines than one can remember, including for some of the world’s deadliest communicable diseases.
Do vaccines work?
Studies suggest with a high degree of confidence that they do. Of course, every vaccine comes with its own list of possible side effects – some minor and common (including pain at the injection site), and some serious, though rare (e.g. anaphylaxis, a potentially life-threatening allergic reaction). But the biggest questions, in determining whether a vaccine will protect you or not, are how quickly the body will respond to pathogen exposure, to what degree, and for how long immunity will last. At the time of writing this article, Pfizer-BioNTech claims that its COVID-19 vaccine is 95% effective and Moderna claims 94.1% effectiveness for its COVID-19 vaccine in preventing the symptomatic coronavirus disease after two doses. Getting vaccinated does not necessarily mean someone cannot still acquire the disease, as vaccinations provide incomplete protection, but the chances of transmitting it to others or developing severe symptoms are significantly reduced. This, in turn, translates to the potential of lower case counts and fatalities. It is worth noting that the length of time that the vaccine will continue to offer protection remains unknown.
From testing to approval, how does a vaccine get to market?
The days of drawing fluid from a milkmaid and injecting it into an 8-year-old, as one might guess, are over. Vaccines must undergo rigorous modelling, projecting, and testing protocols before being approved for use with the general population. A small percentage of vaccines make it from clinical trial through to market (94% chance of failure), but it is estimated that each successful development, for just one vaccine, costs on average $2.8-$3.7 billion USD.
The following steps have been summarized from the Centre for Disease Control, Health Canada, the World Health Organization (WHO), the European Medicines Agency (EMA), and the United States Food and Drug Administration (USFDA) , identifying the steps it takes to go from a concept to an approved safe and effective product:
Step 1: Exploratory stage – research and development of new vaccine.
Step 2: Pre-clinical stage – lab and animal testing.
Step 3: Clinical trials
Phase 1: Small human studies are conducted using healthy adults with no history of exposure in a controlled setting. Clinical safety checks are made throughout and data is recorded on immune response. During this phase, additional variables may be tested, such as subject group, dosage, and immunization schedule. The number of volunteer subjects is usually less than 100 at this stage.
Phase 2: Clinical trials move into the field to test variables on immune response, including age, ethnicity, and gender. Ideally, this phase will solidify safety evaluation and ideal vaccine dosage and schedule. The number of volunteer subjects in this phase expands into the hundreds to thousands.
Phase 3: Random control trials take place to assess the effects of the final formula in the field. This will give the best representation of vaccine efficacy and safety. The sample size is once again reduced to thousands of volunteer subjects.
Step 4: Regulatory review and approval – in most countries, the “sponsor” (potential manufacturer/producer) of a new vaccine product must follow a multi-step approval process, which may include:
- An investigational new drug (IND) application
- Pre-licensure vaccine clinical trials
- A biologics licence application (BLA)
- Inspection of the manufacturing facility
- Presentation of findings to the country’s drug administration board
- Usability testing of product labelling
Step 5: Manufacturing and distribution – A limited number of companies are allowed to manufacture the vaccine. Companies that have received approval from the drug administration board in their country are then permitted to begin production of the product, and distribution to approved outlets.
Step 6: Ongoing monitoring and review – data is analysed from reports of adverse events to confirm the safety and efficacy of the vaccine, and ensuring the benefits continue to outweigh the risks.
There are an estimated 150 COVID-19 vaccines under development around the world with 50 vaccines in clinical trials.
Vaccines don’t grow on trees – what is the cost?
From 2000 through 2018, 35 of the largest pharmaceutical companies reported a cumulative profit of $11.5 trillion USD and a gross profit margin of 76.5%. During these unfamiliar times, however, it would appear many pharmaceutical companies are putting profits aside. Johnson & Johnson has adopted a not-for-profit pricing model for the COVID-19 vaccine. First-out-the-gate manufacturer Pfizer has committed to reduced prices with the understanding that purchasing governments are providing the vaccine for free to the public, though no specific mention of profitability model has been released.
Countries including Canada and the United States have indicated that the COVID-19 vaccines will not come with a financial cost to their citizens. Governments may be footing the bill for the cost of the vaccine, but government funds come from taxpayers, of course. The Government of Canada reports an investment of more than $1 billion CAD to secure vaccines. According to Project Warp Speed (a joint initiative by health organizations in the U.S. to secure COVID-19 treatments and vaccines), the group has received almost $10 billion USD from congress to help achieve their directives. These calculations do not take into consideration the investments made into manufacturing efforts and supplies needed to administer the COVID-19 vaccines.
News outlets have reported that Canada had an initial deal in place for 194 million doses but now more than 400 million on order from a variety of manufacturers, enough for the recommended two-dose series for about five times its population. According to Project Warp Speed, the U.S. has committed to, or has the option of purchasing, 1.2 billion doses (enough for just under twice its population) from various manufacturers. This is dependent on the vaccines obtaining approval for distribution within their given countries. Initial reports from the U.S. are that pharmaceutical companies are charging the governments between $19.50 and $25 USD per dose, of which two doses will be recommended to achieve immunity for the available mRNA vaccines. This could spell a lot of debt and taxes for the U.S. and Canada.
Populous vaccine sentiment by country
With so much skin in the game, projected uptake rates are critical metrics for vaccine producers and public health bodies to consider. For most countries, it is unclear if they intend to make the COVID-19 vaccination mandatory. If they do require vaccination, compliance rates are the next uncertainty.
A recent study of vaccine confidence highlighted the wide range of opinions from around the world. Based on findings from survey data collected from 2015 to 2018, residents of countries in northern and eastern Asia, and Eastern Europe showed the greatest distrust in vaccines. By contrast, those in Africa and South America generally believed vaccines to be safe and effective. North Americans trend toward belief in the efficacy of vaccines and do not stray greatly in either direction from moderate views, when evaluated over time.
According to French marketing firm Institut de Publique Sondage d’Opinion Secteur’s (IPSOS) most recent survey, focusing on a COVID-19 vaccine specifically, which took place during the last week in January 2021 across 15 countries, more respondents were confident about being vaccinated than in an IPSOS survey taken in December. According to the new survey, the United Kingdom shows the highest level of vaccination intent, with 89% of British adults who have not been vaccinated against COVID-19 agreeing they would get a vaccine if it were available.
Among the other countries, intent to take a COVID-19 vaccine:
Brazil (88%), China (85%), Mexico (85%), Italy (80%), Spain (80%), Canada (79%), South Korea (78%), Australia (73%), U.S. (71%), and Germany (68%), Japan (64%), South Africa (61%), France (57%), Russia (42%).
In 11 of the 15 countries surveyed, most of those who agreed that they will receive the vaccine say they plan to do so immediately or within one month once it is available to them:
Mexico (82%), Brazil (79%), and the U.K. (79%), Spain (71%), U.S. (70%), Germany (68%), Canada (67%), Italy (66%), France (59%), Australia (56%), South Africa (55%), China (49%), Japan (39%), Russia (37%), South Korea (28%).
Herd immunity – the key
Whether you support vaccination or prefer to take your chances with natural immunity, you have an important decision ahead. For those who choose not to get a vaccine or are not able to due to eligibility criteria, protection from an infectious disease depends largely on herd immunity, also known as population immunity. Does herd immunity work? Humans have been around for thousands of years and we have only had vaccines for the last couple of centuries, so clearly it works on some level.
Herd immunity can be achieved when the transmission of a disease is prevented by way of immunity from natural infection or vaccination. When you interrupt the chain of infection, and thus the spread, those who are immunologically naïve are protected. The threshold to reach effective herd immunity differs by infectious disease, but typically ranges from 50-90% of the population. At time of writing, the herd immunity threshold for COVID-19 is unknown. Communities may be able to slow the spread of COVID-19 by public health orders and lockdowns, but if there is going to be progress toward returning to “normal” life, herd immunity holds the key.
The bottom line
As with all research, data is but one viewpoint at a moment in time, based on specific guidelines. How this will play out in real time with the new coronavirus and its variants is yet to be determined. But now that you know more about the vaccine story, past and present, when the COVID-19 vaccine is released in your community, will you be first in line or first to decline?
For the vaccine nerds
If you would like to see how your country stacks up when it comes to the World Health Organization’s (WHO) list of vaccine-preventable disease, check out this monitoring system to see mortality and immunization rates by antigen: https://apps.who.int/immunization_monitoring/globalsummary/countries?countrycriteria%5Bcountry%5D%5B%5D=USA
Great article! I am wondering how they choose human subjects for trials, and also, what type of people volunteer for this potentially risky process. What’s in it for them?
Insightful comment! The populations they perform trials on are supposed to be representative of the general population. I imagine that since vaccines have been around for so long that the risk of potentially fatal side effects is minimal, however, I agree, I would love to see a survey of volunteers and some interviews! I wonder if treatment patient 0 is the scientist who developed the vaccine?