Development of a biodegradable nanoparticle based vaccine for Clostridium difficile infection

Abstract

Clostridium difficile is now considered to be one of the major causes of infectious diarrhea in healthcare systems worldwide C difficile infection is believed to be a toxin-mediated intestinal disease caused mainly by two large exotoxins toxins A and B In this study we constructed a non-toxic recombinant protein rTcdB which consists of residues 1852-2363 of Toxin B receptor binding domain as a potential vaccine candidate rTcdB was encased in nanoparticles (NPs) composed of γ-PGA and chitosan which are made of natural materials biodegradable non-toxic and able to induce a high degree of immune response Moreover the NPs were recently reported as a mucosal adjuvant; it could induce a strong mucosal immunity in the gastrointestinal tract We compared intraperitoneal injection and mucosal vaccination regimens and found that both methods provided mice full protection from lethal dose of C difficile spore challenge Protection was associated with high levels of toxin-neutralizing antibodies and the rTcdB-encapsulating NPs elicited longer-lasting antibody responses than rTcdB with the conventional adjuvant aluminum hydroxide These results suggest that rTcdB is highly immunogenic when encapsulated by the safe and potent vaccine adjuvant NPs In conclusion this study demonstrates that prophylactic parenteral or oral vaccination with rTcdB-encapsulating NPs can provide protection from C difficile infection

Date of Award	2016 Jan 28
Original language	English
Supervisor	I-Hsiu Huang (Supervisor)