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

Brucellosis, a zoonotic disease caused by Brucella, poses significant threats to public health and animal husbandry globally. Traditional Brucella vaccines such as S19 and RB51 have limitations in terms of safety and efficacy, so we conducted a meta-analysis to systematically compare the immunoprotective efficacy of S2308 gene-deleted strains versus conventional vaccines (S19, RB51, A19) in mice. Relevant studies were identified through a systematic literature search, and eligible studies were included for analysis. Pooled analyses were conducted using the mean difference (MD) in post-challenge spleen bacterial load as the effect size. Due to the high heterogeneity observed in the analysis of mouse spleen bacterial load, subgroup analysis and meta-regression were subsequently employed to investigate potential sources of this heterogeneity. Results revealed that the S2308 gene-deleted strain exhibited comparable protective efficacy to traditional vaccines, although its effectiveness was regulated by multiple factors. Heterogeneity mainly originated from mouse strain, age, the functional category of deleted genes, number of deleted genes, and challenge dose. These findings highlight that the future development of next-generation Brucella 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 thus provides a clear roadmap for the development of advanced genetically engineered Brucella vaccines with improved performance.