Oral immunization of mice with recombinant Lactococcus lactis expressing Cu,Zn superoxide dismutase of Brucella abortus triggers protective immunity

Abstract

Brucella infections mainly occur through mucosal surfaces. Thus, the development of mucosal administered vaccines could be instrumental for the control of brucellosis. Here, we evaluated the usefulness of recombinant Lactococcus lactis secreting Brucella abortus Cu-Zn superoxide dismutase (SOD) as oral antigen delivery system, when administered alone or in combination with L. lactis expressing IL-12. To this end, mice were vaccinated by oral route with L. lactis NZ9000 transformed with pSEC derivatives encoding for SOD (pSEC:SOD) and IL-12 (pSEC:scIL-12). In animals receiving L. lactis pSEC:SOD alone, anti-SOD-specific IgM antibodies were detected in sera at day 28 post-vaccination, together with an IgG2a dominated IgG response. SOD-specific sIgA was also detected in nasal and bronchoalveolar lavages. In addition, T-cell-proliferative responses upon re-stimulation with either recombinant SOD or crude Brucella protein extracts were observed up to 6 months after the last boost, suggesting the induction of long term memory. Vaccinated animals were also protected against challenge with the virulent B. abortus 2308 strain. Responses were mildly improved when L. lactis pSEC:SOD was co-administered with L. lactis pSEC:scIL-12. These results indicated that vaccines based on lactococci-derived live carriers are promising interventions against B. abortus infections.