Brucella melitensis Rev. 1 living attenuated vaccine: Stability of markers, residual virulence and immunogenicity in mice

Bosseray, Nicole

doi:10.1016/s1045-1056(05)80025-9

Cited by 39 publications

(27 citation statements)

References 8 publications

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“…This is troublesome because, depending on the challenge, no absolute protection is achieved with these vaccines and, therefore, serological tests do not always elucidate whether a given animal is infected or simply shows postvaccinal antibodies. Rev 1 shows some additional negative traits: it is resistant to streptomycin, one of the antibiotics of choice used to treat brucellosis in combination with tetracyclines [13], and it is relatively unstable thus requiring careful standardization to prevent variations in safety and effectiveness [10,17,18,52]. The rate of abortion caused by S19 is low (less than 1% in a large study involving over 10 000 cows which were 7 to 8 months pregnant [84]) but that of Rev 1 can be higher, particularly in association with some of its variants [17].…”

Section: Rough Brucellosis Vaccinesmentioning

confidence: 99%

“…The method allows the prediction of the safety and immunogenicity of Rev 1 and S19 seed stocks on the values of two complementary parameters: the residual virulence (i.e., the persistence in the spleen determined as the Recovery Time 50 [RT 50 ] of the vaccine) and the immunogenicity (i.e., the ability to protect against a challenge with a virulent strain determined as the number of virulent bacteria in the spleen). These parameters are measured under a tightly defined set of experimental conditions, including the number and breed of the animals, route of inoculation, doses (vaccine and challenge), challenge strain, and time intervals at which the number of colony forming units (CFU) in spleens are determined [18,52]. This particular mouse model discriminates both insufficiently attenuated and ineffective Rev 1 and S19 from useful seed stocks by using as controls the RT 50 and immunogenicity of reference stocks of the respective vaccines known to perform satisfactorily in sheep and cattle.…”

Section: The Mouse Modelmentioning

confidence: 99%

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Rough vaccines in animal brucellosis: Structural and genetic basis and present status

Grilló²,

et al. 2004

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-Brucellosis control and eradication requires serological tests and vaccines. Effective classical vaccines (S19 in cattle and Rev 1 in small ruminants), however, induce antibodies to the O-polysaccharide of the lipopolysaccharide which may be difficult to distinguish from those resulting from infection and may thus complicate diagnosis. Rough attenuated mutants lack the O-polysaccharide and would solve this problem if eliciting protective immunity; the empirically obtained rough mutants 45/20 and RB51 have been used as vaccines. Strain 45/20 is reportedly unstable and it is not presently used. RB51 is increasingly used instead of S19 in some countries but it is rifampicin resistant and its effectiveness is controversial. Some controlled experiments have found good or absolute protection in adult cattle vaccinated orally (full dose) or subcutaneously (reduced dose) and in one field experiment, RB51 was reported to afford absolute protection to calves and to perform better than S19. Controlled experiments in calves, however, have shown reduced doses of RB51 to be ineffective, full doses only partially effective, and RB51 less effective than S19 against severe challenges. Moreover, other observations suggest that RB51 is ineffective when prevalence is high. RB51 is not useful in sheep and evidence in goats is preliminary and contradictory. Rough mutants obtained by molecular biology methods on the knowledge of the genetics and structure of Brucella lipopolysaccharide may offer alternatives. The B. abortus manB core (rfbK) mutant seems promising in cattle, and analyses in mice suggest that mutations affecting only the O-polysaccharide result in better vaccines than those affecting both core and O-polysaccharide. Possible uses of rough vaccines also include boosting immunity by revaccination but solid evidence on its effectiveness, safety and practicality is not available.

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Section: Rough Brucellosis Vaccinesmentioning

confidence: 99%

Section: The Mouse Modelmentioning

confidence: 99%

Rough vaccines in animal brucellosis: Structural and genetic basis and present status

Grilló²,

et al. 2004

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“…These characteristics, plus the presence of the Tn5 insert in the corresponding restriction fragment, were routinely examined for the isolates at each of the sampling intervals (see below). RT 50 was calculated according to the method of Bosseray (1991) and Bosseray et al (1984). To this end, groups of 32 female Swiss outbred CD-1 mice six weeks of age were subcutaneously inoculated approximately with 1 × 10 8 CFU in 0.1 ml of PBS (exact doses were retrospectively assessed).…”

Section: Virulence Assaysmentioning

confidence: 99%

A two‐component regulatory system playing a critical role in plant pathogens and endosymbionts is present in Brucella abortus and controls cell invasion and virulence

Sola‐Landa

Pizarro‐Cerdá

Grilló

et al. 1998

Molecular Microbiology

324

276

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SummaryTwo mutants showing increased sensitivity to polycations and surfactants were obtained by transposon mutagenesis of virulent Brucella abortus 2308 Nal r . These mutants showed no obvious in vitro growth defects and produced smooth-type lipopolysaccharides. However, they hardly multiplied or persisted in mouse spleens, displayed reduced invasiveness in macrophages and HeLa cells, lost the ability to inhibit lysosome fusion and were unable to replicate intracellularly. Subsequent DNA analyses identified a two-component regulatory system [Brucella virulence related (Bvr)] with a regulatory (BvrR) and sensory (BvrS) protein. Cloning of bvrR in the BvrR-deficient mutant restored the resistance to polycations and, in part, the invasiveness and the ability to multiply intracellularly. BvrR and BvrS were highly similar (87-89% and 70-80% respectively) to the regulatory and sensory proteins of the chromosomally encoded Rhizobium meliloti ChvI-ExoS and Agrobacterium tumefaciens ChvI-ChvG systems previously shown to be critical for endosymbiosis and pathogenicity in plants. Divergence among the three sensory proteins was located mostly within a periplasmic domain probably involved in stimulus sensing. As B. abortus, R. meliloti and A. tumefaciens are phylogenetically related, these observations suggest that these systems have a common ancestor that has evolved to sense stimuli in plant and animal microbial environments.

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“…It was shown that although the vaccine prevented abortion, it did not provide protection against infection. Bosseray demonstrated that different lots of Rev.1 vaccines showed variable immunogenicity in mice according to their level of virulence (5,6). This study emphasized the instability of the biological properties of the vaccine strain, stressing the need for stringent control of vaccine production (7).…”

mentioning

confidence: 98%

Identification of the Brucella melitensis Vaccine Strain Rev.1 in Animals and Humans in Israel by PCR Analysis of the Pst I Site Polymorphism of Its omp2 Gene

Bardenstein¹,

Mandelboim²,

Ficht

et al. 2002

J Clin Microbiol

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Adverse effects of strain persistence and secretion in milk have been encountered with the Brucella melitensis vaccine strain Rev.1. Field isolates obtained from vaccinated animals and from a human resembled the vaccine strain Rev.1 by conventional bacteriological tests. The lack of a specific molecular marker that could specifically characterize the commercial vaccine strain prevented confirmation of the homology of the Rev.1-like field isolates to the vaccine strain. The composition of the omp2 locus from two gene copies with differences in their PstI restriction endonuclease sites was used to establish an epidemiologic fingerprint for the omp2 gene in the Rev.1 vaccine strain. Primers designed to amplify DNA sequences that overlap the PstI site revealed a single 282-bp DNA band common to all Brucella spp. Agarose gel electrophoresis of the PstI digests of the PCR products from strains 16M and the vaccine strain Rev.1 revealed a distinctive profile that included three bands: one band for the intact 282-bp fragment amplified from omp2a and two bands resulting from the digestion of the amplified omp2b gene fragment, 238-and 44-bp DNA fragments, respectively. Amplified fragments of 37 Rev.1-like isolates, including 2 human isolates, also exhibited this pattern. In contrast, DNA digests of all other Israeli field isolates, including atypical B. melitensis biotype 1 and representatives of the biotype 2 and 3 isolates, produced two bands of 238 and 44 bp, respectively, corresponding with the digestion of both omp2a and omp2b genes. This method facilitates identification of the Rev.1 vaccine strain in both animals and humans in Israel.

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Brucella melitensis Rev. 1 living attenuated vaccine: Stability of markers, residual virulence and immunogenicity in mice

Cited by 39 publications

References 8 publications

Rough vaccines in animal brucellosis: Structural and genetic basis and present status

Rough vaccines in animal brucellosis: Structural and genetic basis and present status

A two‐component regulatory system playing a critical role in plant pathogens and endosymbionts is present in Brucella abortus and controls cell invasion and virulence

Identification of the Brucella melitensis Vaccine Strain Rev.1 in Animals and Humans in Israel by PCR Analysis of the Pst I Site Polymorphism of Its omp2 Gene

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