<b>PRISMA checklists</b>

Brucellosis is a major zoonosis that threatens public health and livestock production worldwide. Although conventional live vaccines, including S19, RB51, and A19, are widely used, their application is limited by safety concerns and field-related constraints. Numerous <i>Brucella abortus</i> S2308-derived gene-deletion mutants have been developed as vaccine candidates; however, their protective efficacy relative to conventional vaccines remains unclear.In this meta-analysis, fifteen studies were included, and random-effects models, subgroup analyses, and meta-regression were applied to compare the protective efficacy of <i>Brucella abortus</i> S2308-derived gene-deletion mutants with that of conventional vaccines and to evaluate whether deleted gene function was associated with differences in protection. The pooled effect showed no statistically significant difference in protective efficacy between S2308-derived mutants and conventional vaccines (MD = 0.38, 95% CI:−0.07 to 0.84; p = 0.10), although substantial heterogeneity was observed (I²= 95.38%). This heterogeneity was partially explained by mouse strain, mouse age, functional categories of deleted genes, number of deletions, and challenge dose. Mutants targeting signal-regulatory genes tended to be associated with lower splenic bacterial loads than those targeting genes involved in lipopolysaccharide (LPS) biosynthesis. Overall, current evidence indicates that S2308-derived gene-deletion mutants provide protection broadly comparable to that of conventional <i>Brucella</i> vaccines in mice, while signal-regulatory gene deletion mutants may represent promising candidates for future vaccine development and warrant further evaluation in target livestock models.