While Hospital-Acquired C difficile Cases Have Decreased, Community-Acquired Cases Have Risen

In the final part of our interview with Joseph Zackular, PhD we focused on the decline of hospital-onset C difficile infections, which has been attributed to improved infection control measures, and the potential for a new vaccine. The vaccine platform, currently in pre-clinical trials, aims to tackle C difficile's complexity with mRNA technology, offering promising immunogenicity even at low doses. The conversation highlighted the need for ongoing epidemiological studies to better define the target population for this vaccine.

Zackular addressed the challenge of identifying who should be targeted for vaccination, particularly as C difficile affects healthcare settings and the community. “One of the things about C diff, at least traditionally, when we’re thinking about healthcare-associated C diff, is that we know who’s at the highest risk of getting a C diff infection. If you're in the healthcare setting for extended periods of time, in long-term care facilities like nursing homes, have comorbidities, or are on antibiotics, you are at a heightened risk for getting C diff,” he explained. “Maybe, unlike some like a viral infection like COVID, we can't really predict who's going to get sick, but with C diff, you can at least predict who will be at the highest risk. And so I think that gives us an opportunity, prophylactically, to vaccinate.”

Despite the decrease in hospital-onset infections, the rise of community-acquired C difficile infections presents new challenges. “But if you’ve been able to see the new data from the CDC, they’ve reported a couple meetings, overall numbers of C diff haven’t gone down, and that’s because community-associated C diff has gone up at the same time as healthcare-associated C diff has gone down,” Zackular said. “And so that gets a little bit more tricky, because what are the risk factors for community-onset C diff? And we don’t really know that. That hasn’t been studied as well.” He emphasized that ongoing studies are needed to better understand these risk factors and refine the targeting for prophylactic vaccination as the epidemiology of C diff continues to evolve.

Zackular also shared his excitement about the broader potential of mRNA technology in treating complicated infections. “The ability of this vaccine platform to take a well-rounded approach to try to tackle a complicated infection with multiple lifestyles and virulence factors and toxins, as well as the fact that, you know, the immunogenicity is just really phenomenal with these mRNA vaccines, and that gives us a real opportunity, even with these low doses that we’re using, and it overcomes some of the negative effects that the toxins have in our own immune system,” Zackular said. He explained that this ability to overcome immune suppression caused by C difficile toxins is a key benefit of the mRNA platform.

Zackular concluded by looking ahead to the future of the vaccine and its potential impact. “These initial studies are just the beginning, and we’re continuing to improve or hoping to take these into patients soon,” he said. As the research progresses, Zackular is hopeful that the mRNA vaccine could help prevent and treat C difficile infections, both in healthcare settings and the broader community.