One of the most common questions we receive at the Montgomery County Health Department is, “how is it possible for COVID-19 vaccines to be safe when they were produced so quickly; haven’t other vaccines taken a lot longer to be approved for use?” Certainly, the name “Operation Warp Speed,” can cause one to pause when deciding whether or not to get vaccinated for COVID-19.
While it is true that historically, vaccines have typically taken 10-15 years of development, testing, and approval to reach patients, there was a perfect storm of circumstances that came into play with COVID-19 vaccines. There were financial considerations, how the clinical studies were conducted, the rapid spread of COVID-19, the vaccine technologies that were utilized, and finally, the manufacture of the vaccines.
It’s important to understand that few pharmaceutical companies produce vaccines. The research, development, and approval processes are difficult, expensive, and the potential legal liability is substantial. The return on investment is low. Each step in the process requires a go/no-go decision before proceeding to the next step.
A company therefore needs a lot of cash if it is going to attempt to manufacture a vaccine. Six major COVID-19 vaccine development programs received $11 billion from Operation Warp Speed as of last October. BioNTech, the company that partnered with Pfizer, received $445 million from the German government. So, the pharmaceutical companies were able to proceed full speed ahead without worrying about financial risk.
Clinical vaccine studies are not only expensive to execute, they usually take a long time to complete. Studies consist of three phases. Phase 1 is done to see if the vaccine produces the intended immune response. It is also a safety trial to see if it causes side effects, known as reactogenicity. People in the trial may develop symptoms or may have changes internally that would indicate toxicity. These trials usually involve a few dozen people.
If a passes Phase 1, it moves to Phase 2 which looks at how well the vaccine works in the intended population. In this case, does the vaccine prevent the development of symptomatic COVID-19 infection in adults of varying ages, ethnicities, etc.? A Phase 2 trial determines the optimal dose and schedule of when to give the vaccine. Phase 2 trials typically enroll a few hundred to a few thousand subjects.
Phase 3 trials involve randomly enrolling hundreds or thousands of people to see if the vaccine is effective in a larger population and if concerning safety issues develop. Approximately half the subjects in the Phase 3 trial get the real vaccine and the other half receive a placebo. The Pfizer-BioNTech vaccine enrolled 40,000 participants, Moderna had 30,000, and Janssen/Johnson & Johnson had 45,000. All of these study populations were large compared to most vaccine studies.
Recall that a typical vaccine takes 10-15 years from development to being injected into arms. Most of this time is taken up by the clinical trials. The three phases are run back-to-back and companies have to wait for the results of each phase before deciding to proceed to the next. This requires planning the next phase and securing funding. The massive government cash infusion for COVID-19 vaccine development allowed each company to run Phases 2 and 3 simultaneously once the safety data were returned from the Phase 1 trials.
Most vaccine-preventable diseases spread more slowly through the population than SARS-CoV-2, the virus that causes COVID-19. Since SARS-CoV-2 spreads so rapidly, it allowed Phase 2 and 3 trials to be completed much more quickly than with other diseases. This allowed the trial data to be collected and analyzed in record time.
The technologies, or “platforms,” used in the creation of COVID-19 vaccines are not new. All three are designed to cause our bodies to manufacture the “spike protein,” the part of the virus that allows the SARS-CoV-2 virus to attach to and infect our cells.
The Janssen/Johnson & Johnson vaccine utilizes a “viral vector.” Viral vector vaccines have been in use since the 1970s. In this application, a human cold virus (adenovirus) is modified so it can’t cause disease. This virus is used to deliver the instructions to produce the SARS-CoV-2 spike protein to our cells, much like a Trojan Horse.
The Moderna and Pfizer-BioNTech both utilize a messenger RNA (mRNA) platform. The concept for these vaccines started in the 1990s and reached the point that they were waiting to be used when a pandemic virus like SARS-CoV-2 emerged. The genetic instructions to produce the spike protein are encased in a nanoparticle made up of fat and sugar molecules. The fat and sugar are digested by our bodies and the mRNA is degraded in a few hours to a day or so. The mRNA does not enter the nuclei of our cells where our DNA resides and therefore can’t combine with our DNA.
The final part of the puzzle explaining why these vaccines are available so quickly is the manufacturing piece. The infusion of cash from Operation Warp Speed allowed the vaccine manufacturers to start to produce the vaccine long before the results of the clinical trials were known. If a vaccine was found to be unsafe or ineffective, the company could just throw it in the trash without any financial risk.
We hope you can see why the three COVID-19 vaccines that are currently approved by the FDA under emergency use authorizations are safe and effective. Safety was not jeopardized. The foresight of the government under our former president to provide the funding via Operation Warp Speed set the wheels in motion for us to be able to vaccinate our fellow Americans, the best way to get us back to our normal lives as quickly as possible.
Additional educational materials:
• This video was produced by JAMA Network before the vaccines were approved, but is an excellent summary of how all three vaccines work: https://bit.ly/3nqEB3r
• “Here’s how experts know the COVID-19 vaccines are safe,” Los Angeles Times, April 6, 2021. https://bit.ly/3nwl3un
• “Coronavirus mRNA Vaccine Safety and Efficacy,” JAMA Network video, February 19, 2021. https://bit.ly/2S5d3ox
• “Adenovirus-Based Vaccine for COVID-19,” American Society of Gene and Cell Therapy video, April 7, 2021. https://bit.ly/3sW1ZGX
Dr. John Roberts contributed this guest column for the Montgomery County Health Department.
