IntroductionDespite the accessibility of several live attenuated vaccines for animals, currently, there is no licensed vaccine for brucellosis in human populations. Available and confirmed animal vaccines may be harmful and considered inappropriate for humans. Thus, human vaccines for brucellosis are required. We aimed to evaluate the effects of Brucella vaccines on mouse models and discuss the potential mechanisms of these vaccines for the design of the appropriate human vaccines.Materials and methodsA systematic search was carried out in Web of Science, Embase, and PubMed/Medline databases. The following MeSH terms were applied: brucellosis, vaccine, Brucella, and vaccination. The original manuscripts describing the Brucella vaccines on mouse models were included. The review articles, editorials, correspondences, case reports, case series, duplicate publications, and articles with insufficient data were excluded.ResultsOf the 163 full texts that were screened, 17 articles reached to inclusion criteria. Combining the results of these trials revealed a reduction in bacterial load and colonization rate of Brucella in the spleen, an increase in inflammatory markers, especially IFN-γ and IL-4, and the highest levels of antibody classes in vaccinated animals compared to animals challenged with various virulent strains of Brucella. The majority of studies found that different anti-Brucella vaccines induced a significant protective effect in animals challenged with Brucella strains. Additionally, mice were given the highest level of Brucella vaccine protection and significant clearance of Brucella strains when the immunization was delivered via the IP (intraperitoneal) or IP-IN (intranasal) routes.ConclusionBrucella is responsible for half-million new cases globally annually, and the lack of a proper human vaccine poses the risk of brucellosis. A variety of vaccines are used to prevent brucellosis. Subunit vaccines and recombinant human vaccines have higher safety and protective properties. Although vaccination helps brucellosis control, it does not eradicate the disease. Thus, we recommend the following strategies. (a) establishment of a registration system; (b) close monitoring of slaughterhouses, markets, and herds; (c) training veterinarians; (d) legal protection of the consequences of non-compliance with preventive measures.