The COVID-19 virus is covered with spike proteins that it uses to enter human cells. Vaccine manufacturers targeted these proteins when developing the vaccine. When a virus such as COVID-19 enters the body, they attack the cells triggering an immune response. It can take several days for an individual’s body to produce the necessary cells to fight the infection. The immune system uses these cells to “remember” the virus in case an individual gets infected again. Researchers are still trying to determine how long immunity lasts when a person recovers from COVID-19. The COVID-19 vaccine protects the body by producing “memory” cells to develop immunity to the virus.
Pfizer
The Pfizer/BioNTech vaccine is the first in the United States to receive an Emergency Use Authorization (EUA). BioNTech began designing the vaccine in January and partnered with Pfizer to scale up research. The first clinical trial was launched in May where they found that it produced an appropriate immune response against the virus. In July, next stage took place with 30,000 volunteers in the United states, Argentina, Brazil, and Germany. The U.S. trial was then expanded to over 44,000 in September. In the clinical trial, the companies included a diverse population including Black, Latino, and white individuals of all ages.
The vaccine was determined to have an efficacy rate of 95%. The efficacy rate is a measurement during a clinical trial, effectiveness is how well the vaccine works in the real world. To calculate the efficacy rate, researchers compared who got sick between the vaccinated population and the placebo (fake vaccine) population in the clinical trial. Pfizer waited for 170 people to develop symptoms of COVID-19. Of the 170 people, 162 received the placebo shot and 8 received the vaccine. The efficacy rate is then based on the number of people who got sick.
The Pfizer vaccine requires 2 doses, 3 weeks apart.
Moderna
Moderna received EUA from the FDA on December 18, 2020. Like Pfizer and BioNTech, the vaccine uses mRNA to produce immunity. Moderna was the first company in March to begin human trials. After promising preliminary results, the company launched the Phase 3 trial with around 30,000 volunteers. The results showed that of the 196 cases among the trial volunteers, 185 received the placebo and none of the 11 vaccinated volunteers suffered from severe disease. The trial showed that the vaccine has an efficacy rate of 94.1%. The Moderna vaccine requires 2 doses, 4 weeks apart.
Johnson & Johnson
Johnson & Johnson’s vaccine is currently in the midst of the Phase 3 trial. The trial had to paused in October to investigate an adverse reaction in a volunteer, but was resumed 11 days later. There are 45,000 individuals in the trial and initial results are expected in January. Unlike the Moderna and Pfizer vaccine, this one will only require one dose.
How are the vaccines developed?
There are four phases that a vaccine must go through before being released to the public. The vaccines undergo a rigorous process of testing before the FDA approves it for use. The vaccines have been approved so quickly because of government support and urgency.
Preclinical stage
First is the preclinical testing to understand how the vaccine will work. This research-intensive stage involves animal testing in either mice or monkeys to see if it produces an immune response.
Phase 1 Safety Trials
Phase 1 is the first time the vaccine is tested on a small group of adults, usually between 20 to 80 people to evaluate safety and to confirm it produces an immune response.
Phase 2 Expanded Trials
Phase 2 involves hundreds of people, both children and adults to see their response to the vaccine as well as to determine the most effective dose to administer. During this trial, researchers will be able to better determine adverse effects and serious reactions to the vaccine. Various companies combined both Phase 1 and Phase 2 into one phase, Phase 1/2a, to speed up the vaccine timeline.
Phase 3 Efficacy Trial
Phase 3 is the final trial and involves thousands of the people to determine if the vaccine protects against the coronavirus. These trials generally involve about half the participants receiving the vaccine and the rest receiving a placebo. From there, researchers compare who develops symptoms between the vaccinated and placebo populations to determine the efficacy rate. These are randomized controlled studies involving broad demographic groups to generate vital safety data.
Early and Limited Trial
After a successful Phase 3 trial, vaccine manufacturers can submit an application to the U.S. Food and Drug Administration (FDA) for Emergency Use Authorization (EUA). In order to receive an EUA, the FDA must confirm that the potential benefits of a vaccine outweigh the risks. Vaccine manufacturers first submit their analysis of the phase 3 trial as well as all safety data from both phase 1 and 2. FDA also reviews the chemistry, manufacturing, and controls used to produce the vaccine.
Another part of the evaluation involves external scientists and public health experts as part of the Vaccines and Related Biological Products Advisory Committee. This panel holds a public meeting to discuss the safety and effectiveness data to evaluate whether an EUA should be granted. If the advisory committee recommends the vaccine, FDA’s career professional staff of scientists and physicians will determine whether to support an EUA for the vaccine.
Approval
Even after EUA is granted, FDA will continue to monitor the effects of the vaccine and analyzes the results of all the clinical trials. The end result would be a full approval of a COVID-19 vaccine.
Why did the vaccine get approved so quickly?
In May 2020, the Trump Administration launched Operation Warp Speed (OWS), a public-private partnership to accelerate the production of a COVID-19 vaccine. OWS was funded with about $10 billion from the CARES Act, passed by Congress in March. OWS is led by Dr. Moncef Slaoui, a vaccine researcher and former executive of GlaxoSmithKline. The government gave this money to eight pharmaceutical companies including Johnson & Johnson and Moderna for vaccine research, with the anticipation that some of the candidates would not work. Currently, two vaccines (Pfizer and Moderna) have been approved for emergency use while Johnson & Johnson is completing their Phase 3 trial. While Pfizer-BioNTech did not use OWS funding, the federal government pre-bought 100 million doses to distribute.
There are multiple reasons for why the COVID-19 vaccine was developed in record time. First, there has never been such a high demand or urgency for a vaccine. This type of public-private collaboration has never been done before. Next, the government pre-bought vaccines and combined clinical trials when possible. No steps were skipped to expedite the production of the vaccine, rather the FDA was able to simultaneously organize and facilitate clinical trials to speed up the process. Next, in normal vaccine development, manufacturing is scaled up after each trial depending on the results. In this case, vaccine candidates were manufactured while the trials were ongoing, so it was ready to rapid deployment if proven to be safe and effective. This increases financial risk for the government but does not sacrifice efficacy or safety. If the trials showed the vaccine was ineffective, production would simply stop. Numerous experts have verified that no corners were cut when developing the vaccine. Finally, the scientific makeup of this COVID-19 vaccine is different than other vaccines.
