Intranasally administered anti-Brucella subunit vaccine formulation induces protective immune responses against nasal Brucella challenge

The present study was aimed to develop a safe and effective anti-Brucella subunit vaccine for mucosal protection against the respiratory exposure of Brucella infection. A chitosan-based Brucella nasal vaccine (BNV) was formulated using well-known Brucella immunogens, sodC, omp19, BLS and PrpA and tested against nasal Brucella challenge in BALB/c mice. The mice were intra-nasally vaccinated with sterile phosphate buffer saline (PBS), BNV or BNV plus Brucella LPS, and humoral (systemic IgG and mucosal IgA) and cell-mediated immune responses were analyzed. Results showed that mice vaccinated with either BNV or BNV plus LPS elicited significantly (p < 0.05) high IgG and IgA responses compared to the PBS control. The IgG responses were significantly (p < 0.05) higher than IgA levels, which showed almost comparable levels observed in either intestines or in lungs. Furthermore, the IgG and IgA responses against each individual component of the BNV formulation indicated that omp19 induced highest levels of both IgG and IgA levels than the other constituents of BNV formulation. Upon re-stimulation of the splenocytes with Brucella whole cell lysate, significantly (p < 0.05) high IFN-γ levels, lymphocyte proliferation, and CD4+ T cell responses were observed in mice vaccinated with BNV or BNV plus LPS. Upon sub-lethal nasal challenge with wild-type Brucella strain, vaccinated mice showed significant reduction of Brucella recovery in lungs and spleen compared to the PBS control. This study indicates that BNV formulation with or without Brucella LPS efficiently induced humoral and cell-mediated immune responses and conferred significant protection against the sub-lethal Brucella challenge.