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

Toxins

Maria R. Romano¹  Rosanna Leuzzi¹  Emilia Cappelletti²  Marta Tontini¹  Alberto Nilo¹  Daniela Proietti¹  Francesco Berti¹  Paolo Costantino¹  Roberto Adamo¹ 

[1] Novartis Vaccines, Via Fiorentina 1, Siena 53100, Italy; E-Mails:;Novartis Vaccines Institute for Global Health, Via Fiorentina 1, Siena 53100, Italy; E-Mail:

关键词: Clostridium difficile;    glycoconjugate;    PSII polysaccharide;    recombinant toxin fragment;   

DOI  :  10.3390/toxins6041385

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.