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

Castaño-Zubieta, M. Raquel; Rossetti, C; García-González, Daniel G.; Maurizio, Estefanía; Hensel, Martha E.; Rice‐Ficht, Allison C.; Ficht, Thomas A.; Arenas-Gamboa, Ángela M.

doi:10.1016/j.vaccine.2020.11.033

Cited by 6 publications

(4 citation statements)

References 18 publications

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“… 15 Like other Gram-negative organisms, Brucella strains express a lipopolysaccharide (LPS) lacking endotoxin activity. Importantly, Bm∆ vjbR has been shown to be safe in immunocompetent and immunocompromised mice, 16 goats, 17 sheep, 18 and non-human primates. 19 We have also shown that Bm∆ vjbR can combat cancer in a murine model by remodeling the tumor microenvironment (TME) to a pro-inflammatory state.…”

Section: Resultsmentioning

confidence: 99%

A metabolically engineered bacterium controls autoimmunity and inflammation by remodeling the pro-inflammatory microenvironment

et al. 2022

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Immunotherapy has led to impressive advances in the treatment of autoimmune and pro-inflammatory disorders; yet, its clinical outcomes remain limited by a variety of factors including the pro-inflammatory microenvironment (IME). Discovering effective immunomodulatory agents, and the mechanisms by which they control disease, will lead to innovative strategies for enhancing the effectiveness of current immunotherapeutic approaches. We have metabolically engineered an attenuated bacterial strain (i.e., Brucella melitensis 16M ∆ vjbR , Bm∆ vjbR::tnaA ) to produce indole, a tryptophan metabolite that controls the fate and function of regulatory T (T reg ) cells. We demonstrated that treatment with Bm∆ vjbR::tnaA polarized macrophages (Mφ) which produced anti-inflammatory cytokines (e.g., IL-10) and promoted T reg function; moreover, when combined with adoptive cell transfer (ACT) of T reg cells, a single treatment with our engineered bacterial strain dramatically reduced the incidence and score of autoimmune arthritis and decreased joint damage. These findings show how a metabolically engineered bacterium can constitute a powerful vehicle for improving the efficacy of immunotherapy, defeating autoimmunity, and reducing inflammation by remodeling the IME and augmenting T reg cell function.

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Section: Resultsmentioning

confidence: 99%

A metabolically engineered bacterium controls autoimmunity and inflammation by remodeling the pro-inflammatory microenvironment

et al. 2022

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“…Still, the quality of controlled studies depends on several experimental requisites that are not easy to implement ( Table 2 ) and, unfortunately, a good understanding of the methodology established many years ago by workers with extensive experience on animal brucellosis is vanishing. This unfortunate event is shown in recent publications that claim the safety and/or efficacy in cattle of influenza virus vectors carrying genes of Brucella L7/L12 or Omp16 [ 138 , 139 , 140 ], a mutant (wrongly characterized as deleted in the perosamine synthetase gene) in buffaloes [ 141 ] and a 16MΔ vjbR mutant in small ruminants [ 142 , 143 ]. Likewise, some recent meta-analyses of controlled experiments use publications that do not meet the requisites in Table 2 and apply elaborated statistics to data that are not amenable to quantification and statistical comparisons because of their qualitative character.…”

Section: The Conundrums Of Animal Brucellosismentioning

confidence: 99%

Facing the Human and Animal Brucellosis Conundrums: The Forgotten Lessons

2022

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Brucellosis is a major zoonotic disease caused by Brucella species. Historically, the disease received over fifty names until it was recognized as a single entity, illustrating its protean manifestations and intricacies, traits that generated conundrums that have remained or re-emerged since they were first described. Here, we examine confusions concerning the clinical picture, serological diagnosis, and incidence of human brucellosis. We also discuss knowledge gaps and prevalent confusions about animal brucellosis, including brucellosis control strategies, the so-called confirmatory tests, and assumptions about the primary-binding assays and DNA detection methods. We describe how doubtfully characterized vaccines have failed to control brucellosis and emphasize how the requisites of controlled safety and protection experiments are generally overlooked. Finally, we briefly discuss the experience demonstrating that S19 remains the best cattle vaccine, while RB51 fails to validate its claimed properties (protection, differentiating infected and vaccinated animals (DIVA), and safety), offering a strong argument against its current widespread use. These conundrums show that knowledge dealing with brucellosis is lost, and previous experience is overlooked or misinterpreted, as illustrated in a significant number of misguided meta-analyses. In a global context of intensifying livestock breeding, such recurrent oversights threaten to increase the impact of brucellosis.

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“…Consistently, both vjbR mutants are cleared from the spleens of infected mice few weeks p.i. ( 102 , 103 ) and B. melitensis Δ vjbR is safe in its natural host ( 36 , 105 ). In B. melitensis , VjbR regulates the positive transcription of two of the main virulence factors, the type four secretion system (T4SS) encoded by the virB operon, and flagellar genes, during vegetative growth and intracellular survival ( 101 ).…”

Section: Known and Undefined Mechanisms Of B Melitensis ...mentioning

confidence: 99%

Comparative Review of Brucellosis in Small Domestic Ruminants

2022

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Brucella melitensis and Brucella ovis are the primary etiological agents of brucellosis in small domestic ruminants. B. melitensis was first isolated in 1887 by David Bruce in Malta Island from spleens of four soldiers, while B. ovis was originally isolated in Australia and New Zealand in early 1950's from ovine abortion and rams epididymitis. Today, both agents are distributed worldwide: B. melitensis remains endemic and associated with an extensive negative impact on the productivity of flocks in -some regions, and B. ovis is still present in most sheep-raising regions in the world. Despite being species of the same bacterial genus, B. melitensis and B. ovis have extensive differences in their cultural and biochemical characteristics (smooth vs. rough colonial phases, serum and CO2 dependence for in vitro growth, carbohydrate metabolism), host preference (female goat and sheep vs. rams), the outcome of infection (abortion vs. epididymitis), and their zoonotic potential. Some of these differences can be explained at the bacterial genomic level, but the role of the host genome in promoting or preventing interaction with pathogens is largely unknown. Diagnostic techniques and measures to prevent and control brucellosis in small ruminants vary, with B. melitensis having more available tools for detection and prevention than B. ovis. This review summarizes and analyzes current available information on: (1) the similarities and differences between these two etiological agents of brucellosis in small ruminants, (2) the outcomes after their interaction with different preferred hosts and current diagnostic methodologies, (3) the prevention and control measures, and (4) alerting animal producers about the disease and raise awareness in the research community for future innovative activities.

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

Cited by 6 publications

References 18 publications

A metabolically engineered bacterium controls autoimmunity and inflammation by remodeling the pro-inflammatory microenvironment

A metabolically engineered bacterium controls autoimmunity and inflammation by remodeling the pro-inflammatory microenvironment

Facing the Human and Animal Brucellosis Conundrums: The Forgotten Lessons

Comparative Review of Brucellosis in Small Domestic Ruminants

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