Description
Clostridioides difficile is a gram positive, spore forming, toxin producing anaerobe and one of the leading agents of antibiotic associated diarrhea. The Centers for Disease Control and Prevention (CDC) list C. difficile infections as an urgent threat. The disruption of the normal gut microbiota using antibiotics is the main risk factor for infection. This infection is primarily mediated by the production of toxins; TcdA and TcdB, and in some hypervirulent strains a binary toxin (CDT) is also present. C. difficile infections (CDI) can range from mild diarrhea to pseudomembranous colitis and if left untreated can lead to death. Currently, acute infections of CDI are treated with either Metronidazole, Vancomycin, or Fidaxomicin. These antibiotics are non-specific to C. difficile and have the side effect of continually disrupting the normal microbiota of the gut which is essential to provide resistance to CDI. Development of novel preventive measures against CDI are therefore considered a priority. Ongoing work in our lab involve the development of an oral vaccine. In a mouse model of CDI, we previously demonstrated that using a recombinant receptor-binding domain of C. difficile toxin B produced by Escherichia coli (rTcdB) as the antigen was effective in producing robust antigen specific IgA and IgG antibodies. These robust antibody responses to the C. difficile toxin were enough to prevent disease, however, it failed to reduce bacterial burden leaving the potential for asymptomatic spread and relapses of disease. To combat this, we are working on two solutions. First, we wished to test a new pH sensitive polymer (Eudragit®) to coat rTcdB. The controlled release of antigen into the lower gastrointestinal tract might generate a stronger and more robust antibody response. Second, we are also evaluating the immunogenicity using fusion proteins combining rTcdB with C. difficile surface proteins in a mouse model. When screening multiple formulations of encapsulated rTcdB in a mouse model multiple groups had significantly increased antigen specific IgG responses. Our preliminary results demonstrated that Eudragit® encapsulated rTcdB induced positive but relatively low level of antigen specific IgGs when delivered orally. Indicating Eudragit® may not be a good candidate for oral vaccination. We are currently working on modifying the formulations as well as testing the immunogenicity of different fusion proteins. We hypothesize that a two-target approach may decrease the bacterial load and lead to complete protection against CDI.| Period | 15 Feb 2024 |
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| Event title | Oklahoma State University Center for Health Sciences Research Week 2024 |
| Event type | Conference |
| Location | Tulsa, United States, OklahomaShow on map |
| Degree of Recognition | Regional |