What are the prospects for a Clostridiodes difficile vaccine?

The incidence of Clostridiodes difficile infection (CDI) and related hospitalisation has fallen in recent decades, but CDI is still a highly relevant disease and the downward trend may be starting to reverse. [1-3] Unfortunately, two large phase 3 efficacy trials of Clostridiodes difficile toxoid vaccines failed to reach their primary endpoints[4, 5].  Does this spell the end of efforts to develop a prophylactic vaccine for routine use in older adults? I explain here why I think there is light at the end of the tunnel. CDI remains an important public health concern.  in 2021, the population-based hospitalized CDI incidence ranged from 16/100,000 in England to 61/100,000 in Sweden, which were among the few countries to have data for population-based incidence[1].  Given the risk of recurrent disease and complications, the impact of CDI on individuals is substantial.[2, 6]   Much CDI is now community-associated so hospital control measures are likely to have only...