Clostridium difficile TxAC314 and SLP-36kDa enhance the immune response toward a co-administered antigen

Abstract

This study evaluated the in vivo adjuvant activity of two peptides derived from Clostridium difficile: a fragment of the receptor-binding domain of toxin A (TxA(C314)) and a fragment of the 36 kDa surface-layer protein (SLP-36kDa) from strain C253. Their ability to affect the magnitude, distribution and polarization of the immune response against fibronectin-binding protein A (FnbpA), a protective vaccine antigen against Staphylococcus aureus, was evaluated using two different routes of immunization: intranasal and subcutaneous. It was shown that (i) the route of immunization affected the magnitude of the immune response; (ii) both peptides enhanced the production of circulating anti-FnbpA IgG and IgA; (iii) following mucosal immunization TxA(C314) was more effective than SLP-36kDa at inducing antibody in the gastrointestinal tract; (iv) the adjuvant influenced the Th1/Th2 balance; and (v) TxA(C314) was more effective than SLP-36kDa in inducing a cell-mediated response. These studies provide insight into the ability of different C. difficile-derived peptides to differentially affect and polarize the activity of the immune system and on their potential use as adjuvants in newly developed vaccines.