The longevity of protective immunity by other types of COVID-19 vaccines (i.e., the NovaVax Spike protein nanoparticles, or the Chinese killed-virus vaccines) remains uncertain, but the curious finding that the very different mRNA and Ad vector vaccine platforms both fail to achieve the sustained efficacy of other licensed vaccines (e.g., against childhood infections, yellow fever, or smallpox), warrants reflection. Here, CHMP5 is linked to smallpox.