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Wang, Yuan-Kai,Yan, Ya-Xian,Kim, Hyeun Bum,Ju, Xianghong,Zhao, Song,Zhang, Keshan,Tzipori, Saul,Sun, Xingmin TaylorFrancis 2015 Human Vaccines & Immunotherapeutics Vol.11 No.9
<P><I>Clostridium difficile</I> is the major cause of hospital-acquired infectious diarrhea and colitis in developed countries. The pathogenicity of <I>C. difficile</I> is mainly mediated by the release of 2 large potent exotoxins, toxin A (TcdA) and toxin B (TcdB), both of which require neutralization to prevent disease occurrence. We have generated a novel chimeric protein, designated mTcd138, comprised of the glucosyltransferase and cysteine proteinase domains of TcdB and the receptor binding domain of TcdA and expressed it in <I>Bacillus megaterium</I>. To ensure that mTcd138 is atoxic, 2 point mutations were introduced to the glucosyltransferase domain of TcdB, which essentially eliminates toxicity of mTcd138. Parenteral immunizations of mice and hamsters with mTcd138 induced protective antibodies to both toxins and provided protection against infection with the hyper-virulent <I>C. difficile</I> strain UK6.</P>
Hyperimmune Bovine Colostrum as a Novel Therapy to Combat <i>Clostridium difficile</i> Infection
Sponseller, Jerlyn K.,Steele, Jennifer A.,Schmidt, Diane J.,Kim, Hyeun Bum,Beamer, Gillian,Sun, Xingmin,Tzipori, Saul Oxford University Press 2015 The Journal of Infectious Diseases Vol.211 No.8
<P><B><I>Background.</I></B> <I>Clostridium difficile</I> is a primary cause of antibiotic-associated diarrhea that typically develops when gut microbiota is altered. Conventional treatment for <I>C. difficile</I> infection (CDI) is additional antimicrobial administration, which further disrupts normal intestinal microbiota, often resulting in poor treatment outcomes.</P><P><B><I>Methods.</I></B> A pregnant dairy cow was repeatedly immunized with recombinant mutants of toxins A and B produced by <I>C. difficile</I>, and the resultant hyperimmune bovine colostrum (HBC) was evaluated for therapeutic efficacy in gnotobiotic piglets with diarrhea due to CDI. Control piglets received nonimmune colostrum. To determine the impact of HBC on gut microbiota, 1 of 2 groups of piglets transplanted with normal human gut microbiota was treated with HBC.</P><P><B><I>Results.</I></B> Nonimmune colostrum–treated piglets developed moderate to severe diarrhea and colitis. In contrast, HBC-treated piglets had mild or no diarrhea and mild or no colitis. Lyophilization had no detectable impact on HBC efficacy. HBC had no discernible effect on the composition of normal human gut microbiota in the porcine intestinal tract.</P><P><B><I>Conclusions.</I></B> HBC provides an oral, cost-effective, and safe alternative to antibiotic therapy for CDI. By preserving intestinal microbiota, HBC may be more efficacious than antibiotics. Additional studies are warranted to establish HBC as a viable immunotherapeutic agent for human use against CDI.</P>