In 1776, Edward Jenner, an English physician, made the biggest breakthrough in the fight against infectious disease when he created the smallpox vaccine. Smallpox can be traced back to Egyptian mummies who died 3,000 years ago. A scourge upon the world, it killed an average of 400,000 Europeans per year in the 18th century. The Americas were equally ravaged, with Benjamin Franklin also losing a son to the disease. After Jenner’s research, man had a new way to fight back and by 1979, just over 200 years after Jenner’s discovery, smallpox was eradicated. Through the years, science would go on to create more vaccines for diseases such as anthrax, rabies, cholera, typhoid, yellow fever, pertussis, measles, mumps, rubella and others. In 1955, Jonas Salk created the polio vaccine and eliminated the disease in the United States by 1996.
In our arsenal against infectious microorganisms, the vaccine is the greatest weapon we have and today, it remains our great hope to beat COVID-19. At the time of this writing, two vaccines had been developed to beat COVID-19 and administration to the populace had begun in the United Kingdom. It is hoped that the vaccine is effective.
The aim of a vaccine is to give our body’s natural immune system a blueprint to beat a disease once encountered. It is in this way that the population can attain enough immunity to suppress a virus to the point of extinction. In order to be deemed effective, a vaccine must face multiple clinical trials and in order to be distributed and administered, a vaccine must pass legal certification procedures for safety. The usual process can be long, taking between three and ten years from start to finish.
In 1902, vaccines were being produced for multiple diseases and in response, the U.S. Congress passed “an act to regulate the sale of viruses, toxins, and analogous products,” referred to as the Biologics Control Act. This was the first legislation written to control the quality of drugs. The act also created an organization that became today’s National Institutes of Health. Because of the act, the government had the right to control the establishments where vaccines were being produced. After a polio vaccine accident in 1954, the Center for Biologics Evaluation and Research was formed and is now under the umbrella of the Food & Drug Administration.
In the United States, vaccine development follows a standard series of steps.
Step One: Exploration
The first step involves lab research of the disease, usually lasting 2-4 years. Here, scientists identify the antigen they will use to make the vaccine. Antigens include weakened viruses, weakened bacteria, weakened toxins or virus-like particles.
Step Two: Pre-Clinical Studies
Usually involving animal testing, researchers assess the safety of the vaccine and its ability to provoke an immune response. A safe starting dose can be determined by examining the effects on the animal test subjects. Many vaccine candidates never progress beyond this stage because an immune response is never found. This step often lasts 1-2 years.
Step Three: Submitting the Application
Once step 2 is found successful, a sponsor submits an application for an investigational new drug (IND) to the Food and Drug Administration. In it, the manufacturer describes the process used, shows the lab reports and writes out the proposed future study. The FDA must respond to the application within 30 days.
Step Four: Phase I Vaccine Trials
Once approved by the FDA, human trials can begin. The first trial involves only a small group of adults, usually between 20-80 persons. In this phase, the goal is to assess the safety of the vaccine, as well as its effectiveness at producing an immune response. In this trial, the researchers may attempt to infect the vaccinated individuals with a weakened version of the pathogen in question.
Step Five: Phase II Vaccine Trials
These trials involve a bigger group of people who are more representative of the population at risk for the disease. The goal of this phase is to assess safety, vaccine effectiveness, dose size, vaccination schedule and method of inoculation.
Step Six: Phase III Vaccine Trials
Involving thousands of subjects, the vaccine is tested against a placebo in this phase of trials. (The tests are randomized and double-blind.) The goal is to test the safety of the vaccine in a large group of people. Scientists are also watching for any new side effects that may emerge. Surprising side effects often show up in a larger group of people due to the difference in the biology of individuals. Immune response is also measured in this phase.
Step Seven: Approval and Licensure
Once a successful Phase III trial is completed, the developer submits a Biologics License Application to the FDA. The FDA will then inspect the factory where the vaccine will be produced and approve labeling. After licensure, the FDA will continue to monitor production and conduct its own testing of the vaccine.
Step Eight (Optional): Phase IV Vaccine Trials
To improve safety and efficacy, the vaccine developer may continue to conduct studies after vaccine release.
The Final Step: Continued Monitoring (VAERS)
In 1990, the FDA and CDC established the Vaccine Adverse Event Reporting System (VAERS) with the goal “to detect possible signals of adverse events associated with vaccines.” VAERS is a voluntary reporting system in which anyone who suspects the association of a vaccine with an adverse event can report it to the government. After a report, the CDC investigates the event.
Once a vaccine has completed the phases needed to be certified as safe and effective, the developer’s next step is large scale production and distribution. The FDA is constantly monitoring production of the vaccine and has a right to step in if any problems are found. Once the vaccine is being produced, distribution to customers (governments and healthcare facilities) begins. And, in case of a pandemic in which a majority of the populace must receive a vaccine, a vaccination campaign must be designed and implemented.
The vaccine production process is designed for safety and effectiveness. Trials are mandatory and data is always collected. In times of stress, a vaccine can be “fast-tracked” such as the new COVID-19 vaccines, with an expedited trial process. New side-effects could arise, such as the allergic reaction presented by some recipients in the United Kingdom; but, risks aside, if the new vaccines are effective, the world can once again move back to relative normalcy in the next year. No doubt, science will continue the process outlined earlier to find and create a safer and more effective product. It just takes time.
CDC. (2020). Vaccine testing and the approval process. CDC. Retrieved from cdc.gov/vaccines/basics/test-approve.html
History of Vaccines. (2020). Vaccine development, testing, and regulation. History of Vaccines. Retrieved from historyofvaccines.org/content/articles/vaccine-development-testing-and-regulation
Marques, D. & Stegmaier, A. (2020). The race to vaccinate. National Geographic. Special Issue 11.2020.