A Meta-Analysis of the Protective Efficacy of Brucella abortus S2308 Gene-Deletion Mutant Vaccines Compared to Conventional Vaccines in Mice

Brucellosis remains a major zoonotic disease that affects both public health and animal production worldwide. Conventional live vaccines, including S19, RB51, and A19, are commonly used for disease control; however, concerns regarding their safety and performance under field conditions limit their application. Targeted gene deletion in Brucella abortus S2308 has generated multiple candidate vaccine strains, but their protection relative to conventional vaccines has not yet been clearly established. We synthesized evidence from 15 mouse studies to compare the protective performance of S2308-derived gene-deletion mutants with that of conventional vaccines. The pooled estimate did not show a statistically significant difference in splenic bacterial burden after challenge between mutant and conventional vaccine groups (mean difference [MD] = 0.38, 95% CI: −0.07 to 0.84; p = 0.10), although substantial heterogeneity was observed (I2 = 95.38%). Heterogeneity was partially explained by mouse strain, mouse age, the 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, based on post-challenge splenic bacterial burden, current mouse evidence suggests that S2308-derived gene-deletion mutants may reduce bacterial burden to an extent broadly comparable to that achieved by conventional Brucella vaccines in mice. The observed association between signal regulation-related gene deletions and lower splenic bacterial burden should be regarded as exploratory and requires further validation using broader protective endpoints and studies in natural target hosts.