Systematic Review and Meta-Analysis of the Immunoprotective Efficacy of Brucella abortus S2308 Gene-Deletion Mutants Versus Conventional Vaccines in Mice

Brucellosis is a zoonotic disease caused by <i>Brucella</i> species, which poses a significant threat to global public health and the livestock industry. Conventional vaccines, such as S19 and RB51, exhibit limitations in terms of safety and efficacy. To systematically compare the immunoprotective efficacy of the S2308 gene-deletion strain with conventional vaccines—<i>Brucella</i> <i>abortus</i> Strain 19(S19), Brucella <i>abortus</i> Strain RB51(RB51), <i>Brucella </i><i>melitensis </i>Strain A19(A19)in mice, we conducted a meta-analysis. Eligible studies were identified through a systematic literature search, and a pooled analysis was performed using the mean difference (MD) in spleen bacterial load after challenge as the effect size. High heterogeneity was observed across studies, prompting further exploration of sources of heterogeneity through subgroup analysis and meta-regression. Results demonstrated that the S2308 gene-deleted strains provided immunoprotection comparable to that of conventional vaccines, although its efficacy was modulated by multiple factors. Heterogeneity primarily arose from variables such as mouse strain, age, functional category of deleted genes, number of gene deletions, and challenge dose. These findings indicate that the future development of next-generation <i>Brucella</i> genetically engineered vaccines should prioritize targeting signaling-related genes, while immunization regimens must be carefully considered when validating safety and efficacy in standardized animal models and large animals. This study outlines key strategies and optimization directions for advancing the development of next-generation <i>Brucella</i> vaccines.