Yersinia pestis F1
antigen-loaded
poly(DL-lactide-co-glycolide)/
polyethylene glycol (
PEG) (PLGA/PEG)
microspheres were produced using a water-in-oil-in-water
emulsion/
solvent extraction technique and assayed for their percent yield, entrapment efficiency, surface morphology, particle size, zeta potential, in vitro release properties, and in vivo animal protect efficacy. The Y. pestis F1
antigen-loaded
microspheres (mean particle size 3.8 μm) exhibited a high loading capacity (4.5% w/w), yield (85.2%), and entrapment efficiency (38.1%), and presented a controlled in vitro release profile with a low initial burst (18.5%), then continued to release Y. pestis F1
antigen over 70 days. The distribution (%) of Y. pestis F1 on the
microspheres surface, outer layer, and core was 3.1%, 28.9%, and 60.7%, respectively. A steady release rate was noticed to be 0.55 μg Y. pestis F1
antigen/mg
microspheres/day of Y. pestis F1
antigen release maintained for 42 days. The cumulative release amount at the 1st, 28th, and 42nd days was 8.2, 26.7, and 31.0 μg Y. pestis F1
antigen/mg
microspheres, respectively. The 100 times median lethal dose 50% (LD50) of Y. pestis Yokohama-R strain by
intraperitoneal injection challenge in mice test, in which mice received one dose of 40 μg F1
antigen content of PLGA/PEG
microspheres, F1
antigen in Al(
OH)3, and in comparison with F1
antigen in Al(
OH)3
vaccine in two doses, was evaluated after given by subcutaneous immunization of BALB/c mice. The study results show that the greatest survival was observed in the group of mice immunized with one dose of F1
antigen-loaded PLGA/PEG
microspheres, and two doses of F1
antigen in Al(
OH)3
vaccine (100%). In vivo vaccination studies also demonstrated that F1
vaccines microspheres had a protective ability; its steady-state
IgG immune protection in mice plasma dramatic increased from 2 weeks (18,764 ± 3,124) to 7 weeks (126,468 ± 19,176) after vaccination. These findings strongly suggest that F1-antigen loaded
microspheres vaccine offer a new therapeutic strategy in optimizing the
vaccine incorporation and delivery properties of these potential
vaccine targeting carriers.