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Toxins 2014, 6(4), 1385-1396; doi:10.3390/toxins6041385
Article

Recombinant Clostridium difficile Toxin Fragments as Carrier Protein for PSII Surface Polysaccharide Preserve Their Neutralizing Activity

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Received: 6 February 2014; in revised form: 6 March 2014 / Accepted: 9 April 2014 / Published: 22 April 2014
(This article belongs to the Special Issue Toxin-Antibody Interactions)
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Abstract: Clostridium difficile is a Gram-positive bacterium and is the most commonly diagnosed cause of hospital-associated and antimicrobial-associated diarrhea. Despite the emergence of epidemic C. difficile strains having led to an increase in the incidence of the disease, a vaccine against this pathogen is not currently available. C. difficile strains produce two main toxins (TcdA and TcdB) and express three highly complex cell-surface polysaccharides (PSI, PSII and PSIII). PSII is the more abundantly expressed by most C. difficile ribotypes offering the opportunity of the development of a carbohydrate-based vaccine. In this paper, we evaluate the efficacy, in naive mice model, of PSII glycoconjugates where recombinant toxins A and B fragments (TcdA_B2 and TcdB_GT respectively) have been used as carriers. Both glycoconjugates elicited IgG titers anti-PSII although only the TcdB_GT conjugate induced a response comparable to that obtained with CRM197. Moreover, TcdA_B2 and TcdB_GT conjugated to PSII retained the ability to elicit IgG with neutralizing activity against the respective toxins. These results are a crucial proof of concept for the development of glycoconjugate vaccines against C. difficile infection (CDI) that combine different C. difficile antigens to potentially prevent bacterial colonization of the gut and neutralize toxin activity.
Keywords: Clostridium difficile; glycoconjugate; PSII polysaccharide; recombinant toxin fragment Clostridium difficile; glycoconjugate; PSII polysaccharide; recombinant toxin fragment
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Romano, M.R.; Leuzzi, R.; Cappelletti, E.; Tontini, M.; Nilo, A.; Proietti, D.; Berti, F.; Costantino, P.; Adamo, R.; Scarselli, M. Recombinant Clostridium difficile Toxin Fragments as Carrier Protein for PSII Surface Polysaccharide Preserve Their Neutralizing Activity. Toxins 2014, 6, 1385-1396.

AMA Style

Romano MR, Leuzzi R, Cappelletti E, Tontini M, Nilo A, Proietti D, Berti F, Costantino P, Adamo R, Scarselli M. Recombinant Clostridium difficile Toxin Fragments as Carrier Protein for PSII Surface Polysaccharide Preserve Their Neutralizing Activity. Toxins. 2014; 6(4):1385-1396.

Chicago/Turabian Style

Romano, Maria R.; Leuzzi, Rosanna; Cappelletti, Emilia; Tontini, Marta; Nilo, Alberto; Proietti, Daniela; Berti, Francesco; Costantino, Paolo; Adamo, Roberto; Scarselli, Maria. 2014. "Recombinant Clostridium difficile Toxin Fragments as Carrier Protein for PSII Surface Polysaccharide Preserve Their Neutralizing Activity." Toxins 6, no. 4: 1385-1396.



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