According to national polls, a significant fraction of Americans currently remains hesitant to take any of the three approved SARS-CoV-2 vaccines (Pfizer, Moderna, and Johnson & Johnson). I’ve seen several different reasons given, but one common reason is a safety concern. It is the fear that the rapid development and deployment of the SARS-CoV-2 vaccines makes them somehow less safe than other approved vaccines. I suspect that some people believe that speed means a rushed process that bypassed normal steps in vaccine development and didn’t adequately address adverse effects that could be caused by these vaccines. Fortunately, in this case, that is an unfounded belief. Let’s compare vaccine development to building a house. You could build a house by yourself and do all your own work. You would have to design the house, get permits, prepare the site, lay the foundation, do the framing, put in the utilities, complete the exterior, and finish out the interior. At every step, there would be inspections and approvals before the house was ultimately completed. This would take a considerable amount of time, let’s say several years. Now instead of building it yourself, what if you used a contractor with an unlimited budget and the blueprints in hand? The contractor could have large crews working round the clock for each aspect of construction, with different types of crews often working simultaneously to speed up the process. With an unlimited budget, the contractor could purchase building materials and tools at any price rather than waiting for discounts and sales. Using this approach they could build the complete house in several months, many times faster than the solo builder. Yet they still had to have all the same permits and inspections, so the rapidly built house is just as well-done and safe as the slowly built house. This is essentially what happened with the SARS-CoV-2 vaccines. Our government made these vaccines the highest priority and provided the money and resources needed to ensure maximum efficiency in vaccine development.
For most new vaccines there is a need, but not necessarily an urgency. The COVID epidemic is an exception where we faced a global emergency that demanded an immediate response and the most rapid vaccine development possible. Money for labor and supplies was critical, but there were also other steps taken to shorten the overall process without bypassing any of the requisite safety and approval steps. First of all, it was known from previous coronavirus work that the SARS-CoV-2 spike protein would be the most likely candidate for a vaccine, thus eliminating months to years of basic research (like the contractor already having the blueprints and not having to wait for an architect to design the house). Secondly, while the SARS-CoV-2 vaccines are new, the underlying technology behind the vaccines is not. Both mRNA-based vaccines (Pfizer and Moderna) and adenovirus-based vaccines (Johnson & Johnson) were already under development for other diseases. Years of previous research provided a solid background about the basic biology and the general safety of both these vaccine platforms. Using either mRNA or adenovirus as the platform to produce the SARS-CoV-2 spike protein was just a small adjustment to well-understood technologies rather than a major innovation that would have required significant new testing and evaluation. Lastly, there was considerable time saving by overlapping the testing phases and giving the safety reviews at each step the highest priority. Normally clinical trial phases I (initial safety testing), II (safety and small-scale efficacy testing), and III (safety and large-scale efficacy testing) of vaccine testing are done sequentially since each phase is expensive and there is no point in progressing to the next phase if the prior phase fails. Since funding was not an issue, phases I and II were overlapped to save time. Similarly, once enough safety data accumulated from phases I and II, phase III was launched before the early phases were completed. Even before final efficacy was established in phase III, vaccine production and stockpiling began. Normally this would never be done because if the vaccine failed phase III then any existing vaccine stockpiles would be worthless and just a waste of money. Again, given the emergency of the pandemic and no shortage of funds, preemptive production before phase III was completed was a reasonable gamble. Coupled with the rapid staging of the phase I-III trials, each step of the federal oversite by the Food and Drug Administration (FDA) was given the highest priority; rather than waiting in a long queue, COVID vaccine results were given immediate review. This combination of accelerated testing and approval strategies allowed the vaccines to be created, certified, and distributed to the public in record time without any reduction of safety requirements.
On a final note, it is important to recognize that vaccines do have known side effects. Most such adverse effects are mild and include temporary reactions like injection site pain, headaches, and low fevers. Other reactions such as fainting, dizziness, or an allergic response are more significant and may require medical attention. Still, even these more severe effects are transient, generally are easily controlled, and do not result in any long-lasting medical issues. More problematic are the very rare serious adverse effects that may not show up in the limited test populations of the phase I-III trials. Phase IV testing occurs after a vaccine is released to the public. An extremely rare adverse effect may only become apparent once a vaccine enters public distribution and is given to millions of individuals. Both the FDA and the CDC (Centers for Disease Control) monitor released vaccines extensively for any indication of such significant adverse effects. For example, the AstraZeneca vaccine (not yet approved in the U.S.) may have a risk of causing blood clots in some individuals. While unfortunate if true, the overall risk is about 1 in every 250,000 recipients of the vaccine. Similarly, the Johnson & Johnson vaccine is also under investigation for a possible risk of blood clots occurring in about 1 in every million people receiving their vaccine. The Pfizer and Moderna vaccines appear to have a similar rate of severe adverse effects, primarily serious allergic responses that occur in between 1 in 200,000 to 1 in 500,000 individuals. The incidence of serious adverse effects for each of the SARS-CoV-2 vaccines is not atypical for vaccines. Several other common vaccines such as the hepatitis B vaccine and the yearly influenza vaccine have comparable numbers of serious adverse effects. While zero adverse effects would be ideal, the risks from these vaccines are many times lower than the risk of serious illness from the diseases they prevent. For comparison, the risk of dying from SARS-CoV-2 in the United States is about 1 in 600 (562,000 deaths per a population of 331,000,000), making the vaccines hundreds of times safer than risking infection. With around 170,000,000 COVID vaccine doses given in the U.S. and over 700,000,000 doses given worldwide, the safety of these new vaccines is acceptable for the benefits they provide in protecting individuals from COVID and in helping to stop the global pandemic.