Construction of Brucella melitensis ghost as a putative vaccine candidate against re-emerging disease – Brucellosis

Iron is a fundamental element required by most organisms, including Brucella. Several researchers have suggested that the iron response regulator (irr) and rhizobial iron regulator (rirA) genes regulate iron acquisition by Brucella abortus, influencing heme synthesis by and virulence of this pathogen. However, little is known about another Brucella species, Brucella melitensis. In this research, we successfully constructed two mutants: M5-90Δirr and M5-90ΔrirA. The adhesion, invasion, and intracellular survivability of these two mutants were evaluated in RAW264.7 cells infected with 1 × 106 CFU of M5-90Δirr, M5-90ΔrirA, or M5-90. We also tested the sensitivity of cells to hydrogen peroxide and their ability to grow. In addition, the virulence of these two mutants was evaluated in BALB/c mice. The results showed that the ability of these two mutants to invade and adhere inside the murine macrophages RAW264.7 was attenuated but their ability to replicate intracellularly was strengthened, enhancing the resistance to hydrogen peroxide. The M5-90Δirr mutant showed stronger growth ability than the parental strain under iron-limiting conditions. No differences were observed in the number of bacteria in spleen between M5-90 and M5-90Δirr at 7 or 15 days postinfection. However, the number of M5-90ΔrirA in spleen reduced significantly at 15 days postinfection. The splenic index of the M5-90Δirr group is evidently lower than that of M5-90. This is the first report that irr and rirA genes of B. melitensis are associated not only with virulence but also with growth ability. Together, our data suggest that M5-90Δirr is a promising Brucella vaccine candidate.

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Mannosylated chitosan nanoparticles loaded with FliC antigen as a novel vaccine candidate against Brucella melitensis and Brucella abortus infection

Journal of Biotechnology ◽

10.1016/j.jbiotec.2020.01.016 ◽

2020 ◽

Vol 310 ◽

pp. 89-96 ◽

Cited By ~ 4

Author(s):

Zohre Sadeghi ◽

Mahdi Fasihi-Ramandi ◽

Mohammad Azizi ◽

Saeid Bouzari

Keyword(s):

Brucella Abortus ◽

Vaccine Candidate ◽

Brucella Melitensis ◽

Chitosan Nanoparticles

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Protective Efficacy and Safety of Brucella melitensis 16MΔmucRagainst Intraperitoneal and Aerosol Challenge in BALB/c Mice

Infection and Immunity ◽

10.1128/iai.05330-11 ◽

2011 ◽

Vol 79 (9) ◽

pp. 3653-3658 ◽

Cited By ~ 21

Author(s):

A. M. Arenas-Gamboa ◽

A. C. Rice-Ficht ◽

M. M. Kahl-McDonagh ◽

T. A. Ficht

Keyword(s):

Vaccine Candidate ◽

Brucella Melitensis ◽

Protective Efficacy ◽

Significant Degree ◽

Content Type ◽

Degree Of Protection ◽

Worldwide Distribution ◽

Human Use ◽

Identification And Characterization

ABSTRACTBrucellosis is a zoonosis of nearly worldwide distribution. Vaccination against this pathogen is an important control strategy to prevent the disease. Currently licensed vaccine strains used in animals are unacceptable for human use due to undesirable side effects and modest protection. Substantial progress has been made during the past 10 years toward the development of improved vaccines for brucellosis. In part, this has been achieved by the identification and characterization of live attenuated mutants that are safer in the host but still can stimulate an adequate immune response. In the present study, the identification and characterization of themucRmutant (BMEI 1364) as a vaccine candidate for brucellosis was conducted. BALB/c mice were vaccinated intraperitoneally at a dose of 105CFU with the mutant to evaluate safety and protective efficacy against intraperitoneal and aerosol challenge. All animals vaccinated with the vaccine candidate demonstrated a statistically significant degree of protection against both intraperitoneal and aerosol challenge. Safety was revealed by the absence ofBrucellaassociated pathological changes, including splenomegaly, hepatomegaly, or granulomatous disease. These results suggest that the 16MΔmucRvaccine is safe, elicits a strong protective immunity, and should be considered as a promising vaccine candidate for human use.

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Identification of vaccine candidate peptides and harvesting epitopes of Brucella melitensis

The FASEB Journal ◽

10.1096/fasebj.22.1_supplement.855.18 ◽

2008 ◽

Vol 22 (S1) ◽

Author(s):

Marina Durward ◽

Jerome Harms ◽

Carrie Peltz ◽

John Sidney ◽

Alessandro Sette ◽

...

Keyword(s):

Vaccine Candidate ◽

Brucella Melitensis

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Evaluation of a Brucella melitensis mutant deficient in O-polysaccharide export system ATP-binding protein as a rough vaccine candidate

Microbes and Infection ◽

10.1016/j.micinf.2014.06.013 ◽

2014 ◽

Vol 16 (8) ◽

pp. 633-639 ◽

Cited By ~ 4

Author(s):

Zhen Wang ◽

Jian Rui Niu ◽

Xiao Lei Wang ◽

Tong Lei Wu ◽

Jie Cheng ◽

...

Keyword(s):

Vaccine Candidate ◽

Brucella Melitensis ◽

Binding Protein ◽

Atp Binding ◽

Export System ◽

Atp Binding Protein

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Evaluation of the safety profile of the vaccine candidate Brucella melitensis 16MΔvjbR strain in goats

Vaccine ◽

10.1016/j.vaccine.2020.11.033 ◽

2021 ◽

Vol 39 (3) ◽

pp. 617-625

Author(s):

M. Raquel Castaño-Zubieta ◽

Carlos A. Rossetti ◽

Daniel G. García-González ◽

Estefanía Maurizio ◽

Martha E. Hensel ◽

...

Keyword(s):

Safety Profile ◽

Vaccine Candidate ◽

Brucella Melitensis

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Thermostable Cross-Protective Subunit Vaccine against Brucella Species

Clinical and Vaccine Immunology ◽

10.1128/cvi.00447-14 ◽

2014 ◽

Vol 21 (12) ◽

pp. 1681-1688 ◽

Cited By ~ 3

Author(s):

John W. Cherwonogrodzky ◽

Nicole D. Barabé ◽

Michelle L. Grigat ◽

William E. Lee ◽

Robert T. Poirier ◽

...

Keyword(s):

Subunit Vaccine ◽

Vaccine Candidate ◽

Single Injection ◽

Brucella Melitensis ◽

Bacterial Colonization ◽

Brucella Species ◽

Promising Candidate ◽

Content Type ◽

A Subunit ◽

Multiple Strains

ABSTRACTA subunit vaccine candidate was produced fromBrucella suis145 (biovar 4; expressing both the A antigen ofBrucella abortusand the M antigen ofBrucella melitensis). The preparation consisted mostly of polysaccharide (PS; >90% [wt/wt]; both cell-associated PS and exo-PS were combined) and a small amount of protein (1 to 3%) with no apparent nucleic acids. Vaccinated mice were protected (these had a statistically significant reduction in bacterial colonization compared to that of unvaccinated controls) when challenged with representative strains of threeBrucellaspecies most pathogenic for humans, i.e.,B. abortus,B. melitensis, andB. suis. As little as 1 ng of the vaccine, without added adjuvant, protected mice againstB. suis145 infection (5 × 105CFU), and a single injection of 1 μg of this subunit vaccine protected mice fromB. suis145 challenge for at least 14 months. A single immunization induced a serum IgG response toBrucellaantigens that remained elevated for up to 9 weeks. The use of heat (i.e., boiling-water bath, autoclaving) in the vaccine preparation showed that it was thermostable. This method also ensured safety and security. The vaccine produced was immunogenic and highly protective against multiple strains ofBrucellaand represents a promising candidate for further evaluation.

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