Many aspects of Covid-19 and subsequent vaccine development are unprecedented for a vaccine deployed for use in the general population. Some of these includes the following.
1. First to use PEG (polyethylene glycol) in an injection
2. First to use mRNA vaccine technology against an infectious agent
3. First time Moderna has brought any product to market
4. First to have public health officials telling those receiving the vaccination to expect an adverse reaction
5. First to be implemented publicly with nothing more than preliminary efficacy data
6. First vaccine to make no clear claims about reducing infections, transmissibility, or deaths
7. First coronavirus vaccine ever attempted in humans
8. First injection of genetically modified polynucleotides in the general population
Unprecedented. This word has defined so much about 2020 and the pandemic related to SARS-CoV-2. In addition to an unprecedented disease and its global response, COVID-19 also initiated an unprecedented process of vaccine research, production, testing, and public distribution. The sense of urgency around combating the virus led to the creation, in March 2020, of Operation Warp Speed (OWS), then-President Donald Trump’s program to bring a vaccine against COVID-19 to market as quickly as possible(Jacobs and Armstrong, 2020). OWS established a few more unprecedented aspects of COVID-19. First, it brought the US Department of Defense into direct collaboration with US health departments with respect to vaccine distribution (Bonsell, 2021). Second, the National Institutes of Health (NIH) collaborated with the biotechnology company Moderna in bringing an unprecedented type of vaccine against infectious disease to market, one utilizing a technology based on messenger RNA (mRNA) (National Institutes of Health, 2020). The confluence of these unprecedented events has rapidly brought to public awareness the promise and potential of mRNA vaccines as a new weapon against infectious diseases into the future. At the same time, events without precedent are, by definition, without a history and context against which to fully assess risks, hoped-for benefits, safety, and long-term viability as a positive contribution to public health.
Development of mRNA vaccines against infectious disease is unprecedented in many ways. In a 2018 publication sponsored by the Bill and Melinda Gates Foundation, vaccines were divided into three categories: Simple, Complex, and Unprecedented (Young et al., 2018). Simple and Complex vaccines represented standard and modified applications of existing vaccine technologies. Unprecedented represents a category of vaccine against a disease for which there has never before been a suitable vaccine. Vaccines against HIV and malaria are examples. As their analysis indicates, depicted in Figure 1, unprecedented vaccines are expected to take 12.5 years to develop. Even more ominously, they have a 5% estimated chance of making it through Phase II trials (assessing efficacy) and, of that 5%, a 40% chance of making it through Phase III trials (assessing population benefit). In other words, an unprecedented vaccine was predicted to have a 2% probability of success at the stage of a Phase III clinical trial. As the authors bluntly put it, there is a “low probability of success, especially for unprecedented vaccines.”