<i>Brucella melitensis</i> Vaccines: A Systematic Review

Background: <i>Brucella melitensis</i> is recognized as one of the predominant zoonotic pathogens globally. Live-attenuated vaccine Rev 1 is currently the most effective vaccine for controlling <i>B. melitensis</i> in small ruminants. While <i>Brucella</i> inactivated, nanoparticle, and subunit vaccines are less effective and require multiple doses, live-attenuated vaccines are less expensive and more efficacious. Several drawbacks are associated with the administration of current attenuated <i>B. melitensis</i> vaccines, including interference with serological diagnostic tests, inducing abortion in pregnant animals, shedding in milk, and zoonotic infections in humans. In this systematic review, we summarize the current literature (1970–2022) on <i>B. melitensis</i> vaccines and review their advantages and disadvantages in order to support the rationale for a need for new or improved small ruminant brucellosis vaccines. Methods: A systematic search was carried out in Web of Science, CAB Abstracts, and PubMed. The original articles describing the <i>B. melitensis</i> vaccines were included. Review articles, articles not published in English, articles that did not offer full text, editorials, correspondences, case reports, case series, diagnostic tests, duplicate publications, and other <i>Brucella</i> vaccines (e.g., <i>B. abortus</i> and <i>B. suis</i>) were excluded. Results: Out of 3700 studies, we identified 18 articles that evaluated <i>B. meltensis</i> vaccines, including recombinant <i>B. melitensis</i> strains (16MΔhfq, 16MΔTcfSR, M5-90ΔmanB, LVM31, M5-90ΔvjbR, 16MΔmucR, ΔznuA, M5-90Δpgm, M5-90ΔwboA), live <i>B. melitensis</i> strain (Rev 1), nanoparticle vaccines (<i>B. melitensis</i> 16M, <i>B. melitensis</i> OMP 31, FliC protein—Mannosylated Chitosan Nanoparticles (FliC and FliC-MCN), <i>B. melitensis</i> and <i>B. abortus</i> combined, and <i>B. melitensis</i> 16M nanoparticles combined with oligopolysaccharide), subunit vaccines (outer membrane vesicles or outer membrane proteins), and a DNA vaccine based on <i>B. melitensis</i> outer membrane proteins (Omp25 and Omp31). The results from these studies revealed that these vaccines can induce humoral and cellular responses and reduce macrophage survival. However, most of these vaccines were evaluated only in murine models, which may not accurately reflect how they work in natural hosts. Conclusions: The high prevalence of <i>B. melitensis</i> in humans and animals remains an issue in many parts of the world. Human brucellosis can be prevented by controlling brucellosis in livestock using vaccination and test-and-removal strategies. Prospective vaccines have limitations, including interference with serodiagnostics after vaccination, virulence in humans and animals, the requirement of booster vaccinations, and insufficient efficacy in preventing infection or abortion. Moreover, most of these vaccines have been assessed in mice models, which have failed to predict immunogenicity or efficacy in natural hosts. Because of these limitations and the re-emergence of <i>B. melitensis</i> worldwide with a high incidence of human infection, our review suggests a need for additional research into the molecular pathology and immunological properties of <i>B. melitensis</i> infection and the identification of protective epitopes or genes that would allow for the development of improved vaccines for small ruminants.