Alnakhli Naseer

Background: Brucella melitensis is considered one of the most widespread zoonotic pathogens worldwide. Vaccination remains the most cost-effective strategy for controlling B. melitensis infection in small ruminants. Methods: In this study, we evaluated the immunologic responses and protection against experimental challenge in 18 goats vaccinated with either lipopolysaccharide (LPS) from B. melitensis strain 16M (LPS alone), LPS of B. melitensis strain 16M and MONTANIDE™ ISA 61 VG adjuvant (Seppic; 50 Bd national, 92250 La Garenne-Colombes, France) (LPS + ISA 61 VG), or saline as a control. Results: Goats (n = 6) vaccinated with LPS + ISA 61 VG had greater (p < 0.05) antibody responses than those that were nonvaccinated. Our data demonstrate that goats vaccinated with LPS + ISA 61 VG exhibited greater lymphocyte proliferative responses (p < 0.05) to the LPS antigen than those vaccinated with LPS alone at week 12 after vaccination. However, proliferative responses of peripheral blood mononuclear cell (PBMC) from goats vaccinated with LPS + ISA61VG did not differ (p > 0.05) from responses of PBMC from control goats. CD4+, CD8+, and γδ T cells from all vaccinated goats had negligible proliferation and failed to induce antigen-specific IFN-γ production. Control and vaccinated goats did not differ (p > 0.05) in their protection against abortion, uterine, fetal, mammary, or maternal infection. Conclusions: Our data suggests that LPS + ISA 61 VG induces a robust humoral response but negligible cellular responses. Our data also suggest that LPS + ISA 61 VG or LPS alone would not be efficacious for use as a vaccine in goats, but the LPS + ISA 61 VG inoculum may be beneficial as a booster. Additional trials would be necessary to evaluate the vaccine’s efficacy as a booster inoculation for small ruminants.

Background: Brucella melitensis is recognized as one of the predominant zoonotic pathogens globally. Live-attenuated vaccine Rev 1 is currently the most effective vaccine for controlling B. melitensis in small ruminants. While Brucella 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 B. melitensis 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 B. melitensis 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 B. melitensis 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 Brucella vaccines (e.g., B. abortus and B. suis) were excluded. Results: Out of 3700 studies, we identified 18 articles that evaluated B. meltensis vaccines, including recombinant B. melitensis strains (16MΔhfq, 16MΔTcfSR, M5-90ΔmanB, LVM31, M5-90ΔvjbR, 16MΔmucR, ΔznuA, M5-90Δpgm, M5-90ΔwboA), live B. melitensis strain (Rev 1), nanoparticle vaccines (B. melitensis 16M, B. melitensis OMP 31, FliC protein—Mannosylated Chitosan Nanoparticles (FliC and FliC-MCN), B. melitensis and B. abortus combined, and B. melitensis 16M nanoparticles combined with oligopolysaccharide), subunit vaccines (outer membrane vesicles or outer membrane proteins), and a DNA vaccine based on B. melitensis 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 B. melitensis 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 B. melitensis worldwide with a high incidence of human infection, our review suggests a need for additional research into the molecular pathology and immunological properties of B. melitensis infection and the identification of protective epitopes or genes that would allow for the development of improved vaccines for small ruminants.