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For many, it might seem like 2020 has lasted an eternity; but in science things have moved exceptionally fast.
In January, a novel coronavirus was beginning to draw the world’s attention, and within weeks a biological curiosity turned into a global pandemic.
At the start of the global outbreak, experts cautioned that an effective COVID-19 vaccine was likely years away, if one was ever developed. But before the year was out, multiple vaccine candidates were shown to be safe and effective in clinical trials1,2,3, and some countries had started to vaccinate its citizens.
Scientific advances and concerted efforts by researchers and clinicians throughout the world certainly made the COVID-19 vaccine dream a reality, but some have voiced concern over the speed at which this development appeared. Should we be worried about short cuts that may have been taken to achieve this unprecedented achievement?
It turns out that things may not be as they appear when it comes to the speed of COVID-19 vaccine development. The reality is that COVID-19 vaccines are based on years of documented research that created the critical knowledge, infrastructure, and cutting-edge technology that made rapid vaccine production possible.
Back to the Basics
SARS-CoV2, the novel coronavirus that causes COVID-19, is a new infectious agent, but coronaviruses are not. At least 4 different coronaviruses circulate regularly in human populations and cause the “common cold” 4.
Vaccines targeting coronaviruses that cause the common cold have not been aggressively pursued because the relatively mild impact of infection did not warrant the investment of research time, money, and resources, when other more pressing health concerns remain unsolved.
But the SARS outbreak of 2002-2004 created enough of a concern that vaccines for the first SARS coronavirus were actively explored. Aggressive research produced two candidate vaccines that underwent safety testing in Phase I clinical trials5,6.
However, before the contenders could advance through all levels of testing, the SARS outbreak ended, and the threat faded.
Locking the Target
Despite the lack of a tangible vaccine, one key development from SARS vaccine research and clinical trials was the identification of the viral spike protein as a target for vaccine development.
The SARS coronavirus, like some other coronaviruses, has a large spike protein on its surface. Interfering with the protein prevents it from infecting cells and essentially renders the virus harmless. Research into the novel SARS-CoV2 found that it had a similar spike protein whose function was critical for infection. As a result, a target for vaccine development was identified very early in the COVID-19 pandemic, avoiding the prolonged search that is normally required for vaccine creation.
By using data collected from previous research and quickly validating the spike protein as a vaccine target, almost a decade was cut off the typical vaccine development time.
Producing Results
Manufacturing vaccines constitutes a significant time component of development. Creating infrastructure that may be unique to each vaccine is a time consuming and expensive undertaking. In the case of the SARS-CoV2 virus, similarities with the earlier SARS coronavirus allowed for the transfer of existing knowledge into the development pipeline, and production was started very early in the process. Moreover, newer strategies like the use of mRNA-based vaccines greatly sped up development. While the traditional vaccine process that uses proteins to generate the immune response can take more than a year to produce suitable antigens, mRNA vaccines only take weeks. The combination of a pre-existing production framework and novel antigen development techniques allowed for vaccines to be synthesized for testing in March, 2020 – a short 3 months after SARS-CoV2 emerged on the global stage.
Into the Clinic
After pre-clinical animal testing, vaccines move into human trials using a three phase approach. Phase I and II trials typically involve a few hundred participants and take 1-2 years for each phase. These phases test the safety of vaccines in healthy populations and the ability of candidate treatments to elicit an immune response. Safe and effective vaccines are moved into Phase III, which demands a large expansion of time and money. Because Phase III trials are so expensive to run, pharmaceutical companies may slow the process through economic assessments to determine the cost-benefit for the company. These 2-3 year long studies involve several thousand participants and further test both safety and effectiveness of the vaccine is a larger and more diverse population than Phases I and II.
There is no doubt that the normal timelines for Phases I-III were compressed to meet an emergency demand for a COVID-19 vaccine. But time was saved by using interim data from Phase I and II trials to guide the development of Phase III, rather than waiting for Phase I and II to finish before considering Phase III. While all phases ran to completion, the staggered and overlapping periods allowed for simultaneous trials to run, saving valuable time. Finally, additional time was economized when manufacturers began vaccine production before trials were complete. Starting vaccine production before the end of clinical trials is an economic gamble, but one that was justified by the pressing need.
Even with the reduction in time, the typical number of participants – numbering in the tens of thousands for Phase III – was met in all trials. In clinical trials the recruitment of sufficient numbers of people can be a challenge that slows down the process; but with COVID-19, widespread public interest in the creation of effective vaccines helped to quickly attract large numbers of enthusiastic trial participants.
The Roots of the Solution
As 2020 draws to a close, almost 200 vaccine candidates have been produced, including 58 that are in clinical trials7. This astonishing accomplishment for a condition that was only a vague threat 12 months ago is a testament to the power of scientific cooperation. The investment of time and money, and the dedication of research personnel throughout the world, were critical for this remarkable achievement. But one element that is often lost or overlooked in this process was the years of basic, biomedical research that went into understanding the fundamental nature of viruses. Without this foundational research, the development of promising vaccines would still be a faint hope.
References
- 1. FP Polack, SJ Thomas, N Kitchin, J Absalon, et al. N Engl J Med. December 10. 2020. Link here
- 2. LA Jackson, EJ Anderson, NG Rouphael, PC Roberts, et al. N Engl J Med. 383(20): 1920-1931. 2020. Link here
- 3. M Voysey, SAC Clemens, SA Madhi, LY Weckx, et al. Lancet. December 8. S0140- 6736(20)32661-1. 2020. Link here
- 4. J Cui, F Li, ZL Shi. Cui J et al. Nat Rev Microbiol. 17(3): 181–192. 2019. Link here
- 5. JE Martin, MK Louder, LA Holman, IJ Gordon, et al. Vaccine. 26(50): 6338–6343. 2008. Link here
- 6. JT Lin, JS Zhang, N Su, JG Xu, et al. Antivir Ther. 12(7): 1107-13. 2007.
- 7. MD Knoll and C Wonodi. Lancet. December 8: S0140-6736(20)32623-4. 2020. Link here
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