Development of an auxotrophic, live-attenuated Brucella suis vaccine strain capable of expressing multimeric GnRH

Smith, G.P.; Jain-Gupta, Neeta; Alqublan, Hamzeh; Dorneles, Elaine Maria Seles; Boyle, S.M.; Sriranganathan, Nammalwar

doi:10.1016/j.vaccine.2018.12.070

Cited by 4 publications

(4 citation statements)

References 19 publications

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“…However, the reference S19 vaccine (IV) yielded better results [ 22 ]. Later, a VTRS1 homologue (VTRS2) created in a B. suis biovar 1 (strain 1330) over-expressing the potentially immunocontraceptive multimeric GnRH protein was developed but this construct did not afford protection against B. suis 1330, even after a booster administration [ 23 ]. Also following the R vaccine approach, a B. suis biovar 1 R mutant in pgm (Figure 1 B) reduced spleen colonization in mice challenged with B. suis 1330, but no reference vaccine control was included [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

“…B. abortus and B. melitensis R mutants defective in the O-chain or in the O-chain plus core sugars of the LPS are attenuated and have been extensively investigated as a way to diminish the interference of ruminant vaccines in standard serological tests [ 17 – 20 ]. However, only Pgm (phosphoglucomutase involved in the production of the UDP-glucose involved in bridging the LPS core to the O-chain and in the synthesis of the periplasmic glucans [ 21 ]) and WboA (O-chain glycosyltransferase) have been mutated for developing a B. suis vaccine, either in a B. suis bv1 strain [ 21 – 23 ] or in B. neotomae [ 24 ]. Whereas both types of mutants yielded some protection in mice (see “ Discussion ”), both are made in brucellae that are infectious for humans and do not fully explore the possibilities offered by our current understanding of the genetics and structure of Brucella LPS.…”

Section: Introductionmentioning

confidence: 99%

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Development of attenuated live vaccine candidates against swine brucellosis in a non-zoonotic B. suis biovar 2 background

Aragón-Aranda

Miguel

Lázaro-Antón

et al. 2020

Vet Res

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Brucella is a genus of gram-negative bacteria that cause brucellosis. B. abortus and B. melitensis infect domestic ruminants while B. suis (biovars 1-3) infect swine, and all these bacteria but B. suis biovar 2 are zoonotic. Live attenuated B. abortus S19 and B. melitensis Rev1 are effective vaccines in domestic ruminants, though both can infect humans. However, there is no swine brucellosis vaccine. Here, we investigated the potential use as vaccines of B. suis biovar 2 rough (R) lipopolysaccharide (LPS) mutants totally lacking O-chain (Bs2ΔwbkF) or only producing internal O-chain precursors (Bs2Δwzm) and mutants with a smooth (S) LPS defective in the core lateral branch (Bs2ΔwadB and Bs2ΔwadD). We also investigated mutants in the pyruvate phosphate dikinase (Bs2ΔppdK) and phosphoenolpyruvate carboxykinase (Bs2ΔpckA) genes encoding enzymes bridging phosphoenolpyruvate and the tricarboxylic acid cycle. When tested in the OIE mouse model at the recommended R or S vaccine doses (10 8 and 10 5 CFU, respectively), CFU/spleen of all LPS mutants were reduced with respect to the wild type and decreased faster for the R than for the S mutants. At those doses, protection against B. suis was similar for Bs2ΔwbkF, Bs2Δwzm, Bs2ΔwadB and the Rev1 control (10 5 CFU). As described before for B. abortus, B. suis biovar 2 carried a disabled pckA so that a double mutant Bs2ΔppdKΔpckA had the same metabolic phenotype as Bs2ΔppdK and ppdK mutation was enough to generate attenuation. At 10 5 CFU, Bs2ΔppdK also conferred the same protection as Rev1. As compared to other B. suis vaccine candidates described before, the mutants described here simultaneously carry irreversible deletions easy to identify as vaccine markers, lack antibiotic-resistance markers and were obtained in a non-zoonotic background. Since R vaccines should not elicit antibodies to the S-LPS and wzm mutants carry immunogenic O-chain precursors and did not improve Bs2ΔwbkF, the latter seems a better R vaccine candidate than Bs2Δwzm. However, taking into account that all R vaccines interfere in ELISA and other widely used assays, whether Bs2ΔwbkF is advantageous over Bs2ΔwadB or Bs2ΔppdK requires experiments in the natural host.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Development of attenuated live vaccine candidates against swine brucellosis in a non-zoonotic B. suis biovar 2 background

Aragón-Aranda

Miguel

Lázaro-Antón

et al. 2020

Vet Res

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“…The strain VTRS2 expressing mGnRH can elicit a significant IgG immune response against the mGnRH antigen at 4 and 6 weeks post-inoculation. The rough B. suis strain is an effective vaccine candidate in swine ( 34 ). B. suis Δ pgm could stimulate cellular immune responses and induce good levels of protection against the virulent B. suis strain, abortion, heifer colonization, and bacterial excretion in milk.…”

Section: Live-attenuated Vaccinesmentioning

confidence: 99%

Evaluation of Brucellosis Vaccines: A Comprehensive Review

Heidary

Dashtbin

Ghanavati³

et al. 2022

Front. Vet. Sci.

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Brucellosis is a bacterial zoonosis caused by Brucella spp. which can lead to heavy economic losses and severe human diseases. Thus, controlling brucellosis is very important. Due to humans easily gaining brucellosis from animals, animal brucellosis control programs can help the eradication of human brucellosis. There are two popular vaccines against animal brucellosis. Live attenuated Brucella abortus strain 19 (S19 vaccine) is the first effective and most extensively used vaccine for the prevention of brucellosis in cattle. Live attenuated Brucella melitensis strain Rev.1 (Rev.1 vaccine) is the most effective vaccine against caprine and ovine brucellosis. Although these two vaccines provide good immunity for animals against brucellosis, the expense of persistent serological responses is one of the main problems of both vaccines. The advantages and limitations of Brucella vaccines, especially new vaccine candidates, have been less studied. In addition, there is an urgent need for new strategies to control and eradicate this disease. Therefore, this narrative review aims to present an updated overview of the available different types of brucellosis vaccines.

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“…Brucella genus is Gram-negative intracellular microbes that cause brucellosis, which can result in abortion in domestic animals and undulant fever in human. [1] Brucellosis is the most common zoonotic disease and causes considerable economic losses in the world livestock industry; a potential concern also exists about the use of Brucella as bioterrorism weapons. [23] Hence, the development of sensitive and specific molecular diagnostic methods and effective vaccines to eradicate brucellosis are required.…”

Section: Introductionmentioning

confidence: 99%

Optimization and Comparison of Different Methods and Factors for Efficient Transformation of Brucella abortus RB51strain

et al. 2019

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Background: The development of protective vaccines for Brucella spp. has been hampered by the difficulty in transformation of Brucella cells with foreign DNA for genetic manipulation. It seems that the formation of Brucella spheroplasts would increase the efficiency of transformation. The aim of this study was to devise an efficient method for the transformation of Brucella spp. Materials and Methods: At first, spheroplast of Brucella was prepared by glycine and ampicillin induction and transformed using optimized protocols of CaCl 2 , electroporation, and lipofection methods. Then, the efficacy of transformation was compared between the three-mentioned methods. Results: Ampicillin-induced spheroplasts from early-log phase culture of brucella when incubated in a medium-containing 0.2 M sucrose during cell recovery had higher transformation efficiency in three different methods. Comparison of the transformation efficiency of Brucella abortus RB51 using the CaCl 2 , lipofection, and electroporation methods revealed that the transformation efficiency with the lipofection method was significantly higher than with other two methods ( P < 0.05). Conclusions: Lipofection method by lipofectamine 2000 on ampicillin-induced spheroplasts can be a suitable approach for Brucella transformation.

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Development of an auxotrophic, live-attenuated Brucella suis vaccine strain capable of expressing multimeric GnRH

Cited by 4 publications

References 19 publications

Development of attenuated live vaccine candidates against swine brucellosis in a non-zoonotic B. suis biovar 2 background

Development of attenuated live vaccine candidates against swine brucellosis in a non-zoonotic B. suis biovar 2 background

Evaluation of Brucellosis Vaccines: A Comprehensive Review

Optimization and Comparison of Different Methods and Factors for Efficient Transformation of Brucella abortus RB51strain

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