, 1993; Giannasca & Warny, 2004). Vaccines containing formaldehyde-inactivated TcdA and TcdB have been developed. In healthy volunteers, this vaccine induced high levels of specific neutralizing immunoglobulin G (IgG) and some promising initial experience has been gained in a few patients

with recurrent CDI (Sougioultzis et al., 2005). Although the role of antitoxin TSA HDAC chemical structure immunity in protection from CDI is clear, vaccines based on toxins are unlikely to prevent colonization, and carriage and transmission of C. difficile will therefore remain a persistent threat. Hence, a more complete approach against CDI should consider not only the inhibition of toxicity but also the prevention of bacterial colonization (O’Brien et al., 2005). Cwp84 is a cysteine protease of C. difficile, found to be associated with the S-layer proteins (SLPs). This protease is highly immunogenic in patients with C. difficile-associated disease (CDAD) (Pechine et al., 2005), suggesting that Cwp84 could play an important role in the physiopathology of C. difficile. In particular, Cwp84 could contribute to the cleavage of the extracellular matrix host proteins to facilitate the degradation

selleck screening library of host tissue integrity and thus dissemination of the infection (Janoir et al., 2007). In addition, it has been shown recently that Cwp84 plays a role in the maturation of SlpA. The inactivation of the cwp84 gene in C. difficile 630ΔErm resulted in a bacterial phenotype in which only immature, single-chain SlpA comprises the S-layer (Kirby et al., 2009). The role of Cwp84 in the cleavage of the SlpA precursor in the two structural SLPs (HMW and LMW) has been further confirmed (Dang et al., 2010). The SLPs of C. difficile are potential colonization agents thought to be involved in bacteria–host interaction (Drudy et al., 2001; Calabi et al., 2002; Cerquetti et al., 2002). In a recent study, O’Brien Phloretin and colleagues tested whether anti-SLP antibodies, assessed

independent of the toxins, could have a protective effect against CDI in vivo. In fact, a passive immunization using anti-SLP antibodies significantly delays the progress of CDI in a lethal hamster challenge model (O’Brien et al., 2005). The same laboratory tested SLPs as a vaccine component in a series of immunization and challenge experiments with hamsters. None of the regimens tested conferred complete protection of animals and antibody stimulation was variable and generally modest or poor (Ni Eidhin et al., 2008). In a previous study, we showed that the protease Cwp84 of C. difficile used as an immunogen was able to delay the colonization by C. difficile in a human microbiota-associated mouse model (Pechine et al., 2007). The aim of this study was thus to evaluate the C. difficile protease Cwp84 as a vaccine candidate in a hamster model. We observed the kinetics of colonization and animal death after immunization and challenge with C.