Updated on October 17, 2024.
Vaccines save lives—on massive scales. Globally, about 154 million lives were saved in the 50 years between 1974 and 2024 because of vaccination efforts, according to the World Health Organization (WHO).
The COVID-19 vaccines have had an enormous impact on mortality rates from COVID, as well. In just the first two years of vaccines being available in the United States during the pandemic, about 3.2 million lives were saved and 18.5 million hospitalizations were prevented, according to the Centers for Disease Control and Prevention (CDC).
Vaccines are among the most significant advances in modern medicine, but some of the basic concepts have been known since as long ago as the 1400s. The technology came of age in the late 1700s when the first successful vaccine (for smallpox) was created by English physician Dr. Edward Jenner. Since then, the science of vaccine development has blossomed and reached new heights, saving countless lives around the world.
How vaccines are typically developed
The COVID vaccines were developed safely, effectively, and quickly to meet an urgent global need. To understand how their development was similar to—and different from—others, it’s helpful to take a quick look at how vaccines are ordinarily developed.
Like all medicines, vaccines must be tested carefully and extensively to make sure they’re safe. This testing has multiple phases.
Preclinical phase
The first step in creating a new vaccine is to figure out what type of antigen will work best to make the human immune system respond. In short, an antigen tells the immune system whether a substance in the body is harmful or not. All vaccines contain an antigen, which is the active ingredient. Antigens can take one of several forms:
- Small pieces of the disease-causing organism or virus
- Instructions for making small pieces of the virus
- A weakened version of the disease organism
To figure out the best antigen, researchers will often carry out screenings, evaluations, and animal testing. This phase of research does not involve any human testing. Once researchers have found an antigen they think will work, they’ll create an experimental vaccine by combining the antigen with other ingredients. These may include:
- Preservatives to keep the vaccine from being contaminated. (Preservatives are usually not used if the vaccine is stored in one-dose vials.)
- Stabilizers to prevent potential chemical reactions in the vaccine
- Surfactants to keep the ingredients from clumping or settling
- Adjuvants, such as tiny portions of aluminum salts, to help strengthen the body’s immune response to the vaccine. (Not all vaccines include adjuvants.)
- Residuals, which are tiny trace amounts of substances that might have been used during manufacturing
- Diluents, such as sterile water, which dilute (thin out) a vaccine right before it is administered
Every ingredient is tested for safety during the manufacturing process.
Human clinical trials: phase 1
In phase 1, a small group of young adult volunteers in good health are given the vaccine. They are monitored for side effects and to see if their bodies respond to the vaccine with a strong immune response. They’ll also be given different doses to see what size dose will be most effective.
Human clinical trials: phase 2
For this phase, the number of volunteers increases to several hundred people. There might be many trials in phase 2 to test different age groups and vaccine formulations. Often, a control group (consisting of people who do not receive the vaccine) is included to compare their immune status with the immune responses in the vaccinated group.
All trials in phase 2 that involve a control group are double-blinded. This means the people involved in the study (both the scientists and the volunteers) don’t know which people received the actual test vaccine. This helps avoid anyone being influenced by this knowledge and helps prevent mistakes in data reporting and interpretation.
Human clinical trials: phase 3
In phase 3, the volunteer group increases in size once again to thousands of people. This phase will usually see trials all over the world to make sure that the vaccine performs the same way among different populations. As with phase 2, all trials in phase 3 are conducted as double-blind.
Safety and efficacy reviews
After the clinical trials have published their results, officials look through the data. If it meets the extremely high requirements for safety and effectiveness, then it will be approved by each nation’s health authority or government. If not, the researchers must go back to the drawing board.
Monitoring
Once the vaccine has been approved and is being distributed, scientists and industry regulators keep a close eye on its ongoing safety and effectiveness. They also keep track of data about the effect of the vaccine so they can adjust policies for how the vaccine is used. This helps officials make sure the vaccine has the biggest and strongest impact possible.
What was different about the development of the COVID vaccines?
The first COVID vaccine doses began reaching the public just one year after the first COVID-19 case. Compared with other vaccine timelines, this was quite rapid. (Vaccines usually take five to 10 years to get through the clinical trials, approval process, and manufacturing.) This speedy turnaround time gave some people the impression that research must have been rushed and that safety protocols were not followed.
This isn’t the case. Even amid a pandemic with a great deal of urgency around finding a vaccine, scientists don’t skip steps. Instead, they simply speed the process up, without compromising either the science or the safety. It’s called an accelerated vaccine development timeline.
In an accelerated timeline, different phases of clinical trials can be combined. For some COVID vaccines, researchers combined phases 1 and 2. For other vaccines, they combined phases 2 and 3. All of the normal safety and efficacy checks, investigations, reports, reviews, and license processes remained in place and unchanged.
Another reason why research can move more quickly in a pandemic is that the disease is widespread and hard to avoid. In the COVID pandemic, when a clinical trial participant received a vaccine, they’d likely be exposed to COVID soon after in their everyday life. That meant that the success rate of the vaccine could be measured more quickly than for a rarer or harder-to-catch disease.
During the pandemic, people also got ready for the vaccine rollout ahead of time. Normally, scientists and officials involved in manufacturing or shipping vaccines would wait before spending time and money on setting up infrastructure until after phase 3 clinical trials have been reported.
But in the COVID pandemic, there was a big push by both the U.S. government and by investors and manufacturers to start getting ready well before the phase 3 trial findings came out. This meant that vaccines were able to be produced, packed, and shipped on a large scale as soon as they had been approved by the U.S. Food and Administration (FDA).
Using past experience to tackle new challenges
Importantly, the accelerated timeline for the development of the COVID vaccines also benefited from years of research on vaccine development for other emerging infectious diseases. This includes research into other viruses that emerged over past decades, like severe acute respiratory syndrome (SARS) in 2003 and Middle East respiratory syndrome (MERS) in 2012. Like COVID, SARS and MERS are coronaviruses.
This previous research helped pave the way for the two types of COVID vaccines approved for use in the U.S.: mRNA vaccines and protein subunit vaccines.
mRNA vaccines
The Pfizer-BioNTech and Moderna COVID vaccines use a molecule called messenger RNA (or mRNA) to deliver instructions to the cells in our body. In effect, the mRNA used in these vaccines shows cells how to make proteins that mimic the signature spike proteins found on the COVID coronavirus (formally known as SARS-CoV-2). Once that’s happened, the body’s immune system kicks in, launching an immune response and creating disease-fighting antibodies that can tell the body to destroy anything that has those spike proteins—including SARS-CoV-2.
Even though the vaccines for COVID were the first commercial vaccines to use mRNA, the technology itself is not new. Messenger RNA was discovered in the 1960s. The first flu vaccine using mRNA was tested on animals in the 1990s and a rabies vaccine using mRNA was tested on humans in the early 2010s. There was also an mRNA vaccine developed for the Ebola virus, but since Ebola is not a global or U.S.-based disease, it was not developed on a larger scale.
All of this prior research and previous vaccine technology meant that researchers understood how to quickly make an effective and safe mRNA vaccine against SARS-CoV-2.
Protein subunit vaccines
The protein subunit vaccines made by Novavax are the other type of COVID vaccine. Instead of using mRNA to tell cells how to make a spike protein, these types of vaccines use actual spike proteins from the virus (but not the virus itself), along with an adjuvant, to help the immune system launch a strong response. Once your immune system has responded once to the spike protein, it will recognize the full virus in the future and fight it right away if you’re exposed to the disease.
This type of vaccine also has a long history. It has been used for decades before the COVID pandemic in hepatitis B vaccines and it is also used in whooping cough vaccines.
The bottom line: COVID vaccines are safe
The vaccines approved by the FDA are both safe and effective. After the rollout of the COVID vaccines, the safety monitoring phase was the most stringent and comprehensive in the history of the U.S., according to the CDC.
In fact, safety monitoring has never stopped. As long as new or updated vaccines are being developed, they will continue to be closely and comprehensively monitored for safety.
The CDC recommends that everyone ages six months and older get an updated COVID vaccine made by an FDA-approved manufacturer. Depending on a person’s age, health profile, and previous vaccination experience, more than one dose may be needed.
Both the 2024-2025 formula mRNA vaccines made by Moderna and Pfizer-BioNTech and the 2024-2025 protein subunit vaccine made by Novavax were approved in August 2024.
