Abstract
Introduction:
Clostridium perfringens ε toxin (ETX), a category B biological weapon, causes fatal enterotoxemia in livestock. Vaccination is an effective way to prevent ETX intoxication.
Methods:
A cell membrane-encapsulated nanoparticle vaccine was prepared that adsorbed ASP-ETX (Ov-ASP-1 and epsilon toxin fusion protein) with a targeting effect on B cells and was loaded with the ETXY196E mutant protein (MNP-ASP-ETX). The antigen presentation efficiency of the nanoparticle vaccine was monitored through in vitro cell experiments and in vivo animal experiments, and the biological safety and overall efficacy of the nanoparticle vaccine were evaluated.
Results:
The ETX nanoparticle vaccine showed superior biosafety both in vivo and in vitro, favorable encapsulation efficiency, and a particle size that was easily taken up by antigen-presenting cells. The ETX nanoparticle vaccine released antigens more steadily and exhibited greater lymph node drainage capacity than the traditional aluminum adjuvanted group (ETXY196E + Al). MNP-ASP-ETX elicited antibody titers comparable to the ETXY196E + Al group and induced Th1 and Th2 immune responses. However, the protective effect of the ETX nanoparticle vaccine was slightly weaker than that of ETXY196E + Al. We therefore analyzed immune cell production in the spleen. Although MNP-ASP-ETX increased B-cell levels, indicating that ASP-ETX facilitates the ETX nanoparticle vaccine to target B cells, the effect was not statistically significant, likely owing to the less adsorption of ASP-ETX. The antibody titer and protective effect significantly increased after 2 months, with the magnitude of change surpassing that of ETXY196E + Al and indicating the strong potential of ETX nanoparticle vaccine for providing long-term immunity.
Discussion:
These findings demonstrate that MNP-ASP-ETX can be considered a novel vaccine for the prevention of ETX intoxication and provide new strategies for designing and developing toxin vaccines.