Induction of a Specific Humoral Immune Response by Nasal Delivery of Bcla2ctd of Clostridioides difficile

Abstract

<i>Clostridioides difficile</i>, formerly known as <i>Clostridium difficile</i>, is a spore-forming bacterium considered as the most common cause of nosocomial infections in developed countries. The spore of <i>C. difficile</i> is involved in the transmission of the pathogen and in its first interaction with the host; therefore, a therapeutic approach able to control <i>C. difficile</i> spores would improve the clearance of the infection. The C-terminal (CTD) end of BclA2, a spore surface protein of <i>C. difficile</i> responsible of the interaction with the host intestinal cells, was selected as a putative mucosal antigen. The BclA2 fragment, BclA2_CTD, was purified and used to nasally immunize mice both as a free protein and after adsorption to the spore of <i>Bacillus subtilis</i>, a well-established mucosal delivery vehicle. While the adsorption to spores increased the in vitro stability of BclA2_CTD, in vivo both free and spore-adsorbed BclA2_CTD were able to induce a similar, specific humoral immune response in a murine model. Although in the experimental conditions utilized the immune response was not protective, the induction of specific IgG indicates that free or spore-bound BclA2_CTD could act as a putative mucosal antigen targeting <i>C. difficile</i> spores.