BRUCELLA ABORTUS ROUGH LIVE ATTENUATED VACCINES AGAINST BOVINE BRUCELLOSIS: ASSESSMENT OF SEVEN BRAZILIAN VACCINE CANDIDATES
live vaccine, immunogenicity, residual virulence, mutation, sequencing, DIVA vaccine.
Brucellosis is a zoonotic disease of significant economic and public health concern worldwide, transmitted by bacteria of the genus Brucella spp. Vaccination is a cornerstone for controlling the disease, yet current commercially available vaccines have limitations, including adverse side effects, risk of disease in humans and incomplete differentiation between vaccinated and infected animals. In this study, an experimental study in three steps was conducted to assess the vaccination potential of seven B. abortus mutants that were isolated from cattle in Brazil and were selected as candidates based on their genetic profiles using whole genome sequencing (WGS). The experimental evaluation of each strain in mice and cattle concentrated on its immunogenicity, residual pathogenicity, and serological cross-reactivity. These evaluations included residual virulence assays in mice, immunogenicity assessments in mice, and diagnostic cross-reactivity tests in cattle. The strains used revealed mutations and deletions in the regions corresponding to loci responsible for the production, insertion, or export of lipopolysaccharide (LPS) in the bacterial cell membrane, an important virulence factor, which suggest an attenuation of these strains and a vaccine potential. The seven rough mutants isolated from cattle in Brazil had their potential as live vaccine evaluated and strain LBAB026 emerged as the most promising candidate, as exhibited immunogenicity comparable to strains RB51 and S19 in mice and did not induced antibodies detected in conventional serological tests. Our results demonstrate the potential of the mutant LBAB026 as a differentiating infected from vaccinated animals (DIVA)-compatible vaccine, non-rifampicin resistant candidate that satisfy the safety and effectiveness requirements in mice and, potentially for bovine brucellosis reduction initiatives. These findings highlight the potential of spontaneous rough B. abortus mutants as safe and efficient tools for controlling bovine brucellosis. Additional in vivo studies are essential to evaluate LBAB026 under field conditions, particularly regarding its protective efficacy, safety, and compatibility with eradication programs. These results contribute to the ongoing development of next-generation vaccines, providing a more targeted and sustainable approach to brucellosis management.