Successful prophylactic against Brucella melitensis using a vaccine candidate consisting of recombinant antigens OMP19 and L7/L12 loaded in a nanoliposomal adjuvant system in a mouse model.

Abstract

Brucellosis is a zoonotic disease caused by the genus Brucella. In the present study, a vaccine candidate composed of two recombinant antigens, OMP19 and L7/L12 of B. melitensis, encapsulated in a Nano Liposomal Adjuvant System (NLAS) was developed. The properties of the nanoparticles were evaluated using dynamic light scattering (DLS) and transmission electron microscopy (TEM). Then, encapsulation efficacy, release profile, immunogenicity, and effectiveness of the vaccine candidate were investigated. The synthesized nanoparticles were monodisperse and spherical in shape with a size of around 123 nm. Although an increase in particle size and polydispersity was observed over the storage time, these changes remained within an optimal range. The encapsulation efficacy of the antigens in NLAS was about 71 % and the release rate of the antigens was approximately 65 %. The liposome-OMP19&L7/L12 formulation induced significant Th1 (IgG2a, IFN-γ, and IL-2) and Th2 (IgG1 and IL-4) immune response. The vaccine formulation showed a higher increase in the IgG2a/IgG1 ratio compared to the protein mixture alone and shifted the responses toward Th1 direction. The use of a subcutaneous injection route for the NLAS-OMP19&L7/L12 did not yield a significant difference in IgA induction compared to the protein mixture alone, suggesting that IgA stimulation might require mucosal administration routes for maximal response. After the first and second protection assay, the liposome-OMP19&L7/L12 formulation showed the highest reduction of B. melitensis in the spleen of mice (2.43 and 1.44 log units of protection) compared to the groups received PBS, liposome alone (0.22 and 0.13), the protein mixture alone (0.6 and 0.5), and B. melitensis Rev.1 vaccine (0.98 and 1.2). These findings suggest that NLAS-OMP19&L7/L12 could be a potential candidate for preventing brucellosis caused by B. melitensis. Further research is needed to explore its clinical application.