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Natalie E. Dean, PhD
It is easy to point to the fact that we don’t have licensed vaccines for severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), or HIV/AIDS as reasons to be discouraged about COVID-19. These diseases have been around longer than COVID-19. In the case of HIV/AIDS, much longer. Is there reason to be worried?
Let me attempt to provide some perspective and even a small dose of optimism. We are not in the same situation here.
First, HIV is a uniquely challenging virus, and it is possible that we may never have an HIV vaccine. HIV attacks the host immune system, making it difficult to design an effective vaccine. It also mutates rapidly, diversifying within a person over the course of their infection. Viral diversity within a single person has been shown to be comparable to viral diversity of influenza across the globe. In comparison, SARS-CoV-2 mutates even more slowly than seasonal influenza, making it a more stable target for vaccines.
Next, SARS caused an explosive outbreak in 2003 (Figure 1). Fortunately, that outbreak was contained, in part because SARS-CoV caused severe illness that was less likely to be missed during tracing, and there was no presymptomatic or asymptomatic transmission. After being contained in 2003, there have been no SARS outbreaks since.
While several SARS vaccine candidates were developed, funding dried up to test them further. In addition, there has been no clear pathway for testing the efficacy of SARS vaccine and getting it approved for use. How can we determine whether a vaccine prevents SARS if there is no SARS to prevent? Thus, these candidates have been stalled at earlier stages of development.
Finally, MERS was first reported in 2012. Since then, there have been regular “spillover” events whereby the virus jumps from the camel reservoir into humans and may transmit directly between humans. Some early MERS outbreaks were explosive, including an exported outbreak in South Korea in 2015. But Saudi Arabia, where the majority of transmission occurs, has made great improvements to its infection control procedures to prevent hospital spread. As a result, recent outbreaks have been much smaller (Figure 2).
Organizations like the Coalition for Epidemic Preparedness Innovations (CEPI) have been funding research for MERS vaccine candidates, but one persistent challenge is identifying strategies to evaluate the efficacy of these vaccines. Along with other researchers involved in the WHO R&D Blueprint, we have discussed potential strategies for a MERS vaccine efficacy trial. But given the relatively low incidence even in high-risk groups (camel workers, their families, healthcare workers), trials could need 100,000-plus participants, which isn’t feasible. As a result, there still isn’t a clear path forward for testing a vaccine and getting it approved by regulators.
Of course we all would be better off with effective SARS, MERS, and HIV/AIDS vaccines. In particular, if we had licensed SARS and MERS vaccines, they could be modified for COVID-19. Indeed, many of these candidates were brought back off the shelf for exactly this purpose. But the fact that approved vaccines for these diseases do not exist reflects other challenges in their development as much as anything else. For COVID-19, with widespread transmission and active funding, we should expect large trials to soon begin testing the many vaccine candidates being pursued in parallel. So if one or more of them works, we should be able to figure this out quickly.
Natalie Dean, PhD, is an assistant professor of biostatistics at the University of Florida in Gainesville. She specializes in emerging infectious diseases and vaccine study design. Follow her on Twitter
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