Brucella ovis lacking a species-specific putative ATP-binding cassette transporter is attenuated but immunogenic in rams

Silva, Ana Patrícia C.; Macêdo, Auricélio A.; Costa, Érica Azevedo; Turchetti, A; Bull, Valquíria; Pessoa, Moisés Sena; Araújo, Márcio Sobreira Silva; Nascimento, Evaldo; Martins‐Filho, Olindo Assis; Paixão, Tatiane Alves da; Santos, Renato L.

doi:10.1016/j.vetmic.2013.09.003

Cited by 17 publications

(27 citation statements)

References 27 publications

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“…Although a recent work has reported the ability of a B. ovis attenuated mutant to induce an immune response in a natural host [36] and another work has analyzed the protective activity of a B. ovis mutant in a murine model [37], the potential of attenuated B. ovis strains as vaccines remains almost unexplored. Two B. ovis mutants defective in Omp25d and Omp22 surface protein, have previously been shown to display attenuated virulence in a mouse model [19,38] and in the present work they were evaluated as homologous live attenuated vaccines, in comparison to heterologous B. melitensis Rev 1, for the prophylaxis of B. ovis infection.…”

Section: Discussionmentioning

confidence: 99%

Evaluation in mice of Brucella ovis attenuated mutants for use as live vaccines against B. ovis infection

Sancho

Tejedor

Sidhu-Muñoz

et al. 2014

Vet Res

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Brucella ovis causes ram contagious epididymitis, a disease for which a specific vaccine is lacking. Attenuated Brucella melitensis Rev 1, used as vaccine against ovine and caprine brucellosis caused by B. melitensis, is also considered the best vaccine available for the prophylaxis of B. ovis infection, but its use for this purpose has serious drawbacks. In this work, two previously characterized B. ovis attenuated mutants (Δomp25d and Δomp22) were evaluated in mice, in comparison with B. melitensis Rev 1, as vaccines against B. ovis. Similarities, but also significant differences, were found regarding the immune response induced by the three vaccines. Mice vaccinated with the B. ovis mutants developed anti-B. ovis antibodies in serum of the IgG1, IgG2a and IgG2b subclasses and their levels were higher than those observed in Rev 1-vaccinated mice. After an antigen stimulus with B. ovis cells, splenocytes obtained from all vaccinated mice secreted similar levels of TNF-α and IL12(p40) and remarkably high amounts of IFN-γ, a crucial cytokine in protective immunity against other Brucella species. By contrast, IL-1α -an enhancer of T cell responses to antigen- was present at higher levels in mice vaccinated with the B. ovis mutants, while IL-10, an anti-inflammatory cytokine, was significantly more abundant in Rev 1-vaccinated mice. Additionally, the B. ovis mutants showed appropriate persistence, limited splenomegaly and protective efficacy against B. ovis similar to that observed with B. melitensis Rev 1. These characteristics encourage their evaluation in the natural host as homologous vaccines for the specific prophylaxis of B. ovis infection.

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Section: Discussionmentioning

confidence: 99%

Evaluation in mice of Brucella ovis attenuated mutants for use as live vaccines against B. ovis infection

Sancho

Tejedor

Sidhu-Muñoz

et al. 2014

Vet Res

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“…Although the mouse model has been extensively used to validate live Brucella vaccine-induced protection (37), results cannot be directly extrapolated to other host species, since even different mouse strains influence the protection results (38). Indeed, we have recently demonstrated that the B. ovis ⌬abcBA strain induces humoral and cellular immune responses in rams that are indistinguishable from those triggered by the parental wild-type strain (24). Thus, the results of the present study encouraged us to pursue additional studies to demonstrate the potential of B. ovis ⌬abcBA as a vaccine candidate in rams, which are the preferential hosts for this pathogen.…”

Section: Discussionmentioning

confidence: 99%

“…Although the substrate of this ABC transporter is not known, it is required for expression of B. ovis virulence proteins, including Omp31, Sod, and the virB-encoded type IV secretion system (23), which is required for B. ovis intracellular survival and in vivo persistence (17). Furthermore, a B. ovis ⌬abcBA strain is capable of triggering humoral and cellular immune responses like the wild-type strain in rams; importantly, however, the mutant strain is not excreted in semen and urine (24). Therefore, this mutant strain has great potential as an attenuated vaccine strain.…”

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confidence: 99%

Protection Provided by an Encapsulated Live Attenuated ΔabcBAStrain of Brucella ovis against Experimental Challenge in a Murine Model

Silva

Macêdo

Silva

et al. 2015

Clin. Vaccine Immunol.

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dThis study aimed to evaluate the Brucella ovis ⌬abcBA strain as a vaccine candidate in the murine model. BALB/c mice were subcutaneously or intraperitoneally immunized with a single dose or three doses of the B. ovis ⌬abcBA strain and then were challenged with wild-type B. ovis. Single or multiple immunizations provided only mild protection, with significantly smaller numbers of wild-type B. ovis CFU in the livers of immunized mice but not in the spleens. Encapsulation of B. ovis ⌬abcBA significantly improved protection against experimental challenges in both BALB/c and C57BL/6 mice. Furthermore, immunization with encapsulated B. ovis ⌬abcBA markedly prevented lesions in the spleens and livers of experimentally challenged mice. These results demonstrated that the encapsulated B. ovis ⌬abcBA strain confers protection to mice; therefore, this strain has potential as a vaccine candidate for rams. Brucella ovis is a facultative, intracellular, Gram-negative coccobacillus (1) that causes economic losses due to its potential to induce reproductive failure in sheep (2, 3). The most important lesions caused by B. ovis in rams are epididymitis and seminal vesiculitis (4), and B. ovis occasionally causes abortion in ewes (5, 6).In spite of attempts to develop safe, effective vaccines (7-10), there is no available vaccine specifically against B. ovis. The ideal vaccine against B. ovis must prevent infection and clinical signs or at least reduce the risk of infection and transmission (11). Rev-1, a live attenuated Brucella melitensis strain, is the most commonly used vaccine against B. melitensis, and it also protects against B. ovis (12). However, the Rev-1 strain retains pathogenic potential, so it is capable of infecting humans. It may cause abortions in ruminants, it may interfere with serological tests, and it is resistant to streptomycin (13,14).Mice have been extensively used as a model for brucellosis, which is very important due to the limitations of experimentation with larger animals (15-18). The murine model has allowed studies for the development of safe, effective brucellosis vaccines (15,19,20).Inactivation of a predicted abcEDCBA-encoded ATP-binding cassette (ABC) transporter of B. ovis (21), which is located in B. ovis pathogenicity island 1 (BOPI-1), results in strong attenuation of this pathogen in the murine model (22). Although the substrate of this ABC transporter is not known, it is required for expression of B. ovis virulence proteins, including Omp31, Sod, and the virB-encoded type IV secretion system (23), which is required for B. ovis intracellular survival and in vivo persistence (17). Furthermore, a B. ovis ⌬abcBA strain is capable of triggering humoral and cellular immune responses like the wild-type strain in rams; importantly, however, the mutant strain is not excreted in semen and urine (24). Therefore, this mutant strain has great potential as an attenuated vaccine strain. However, considering that the ⌬abcBA mutant strain is attenuated at very early stages during infection, resulting in p...

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“…However, the substrates of this particular ABC transporter are still unkown (Silva et al 2014). In spite of its attenuation, B. ovis ΔabcBA triggers humoral and cellular immune responses in rams that are indistinguishable from those triggered by the wild-type parental strain (Silva et al 2013). Therefore, B. ovis ΔabcBA has been tested as an experimental candidate vaccine strain and provided protection in a mouse model of infection (Silva et al 2015a).…”

Section: Introductionmentioning

confidence: 99%

Pathogenic potential of Brucella ovis field isolates with different genotypic profile and protection provided by the vaccine strain B. ovis ΔabcBA against B. ovis field isolates in mice

et al. 2020

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ISSN 0100-736X (Print) ISSN 1678-5150 (Online) RESUMO-[Vacina viva atenuada Brucella ovisΔabcBA encapsulada protege camundongos frente a desafios de B. ovis isoladas de campo.] Brucella ovis é responsável por perdas econômicas e reprodutivas em rebanhos ovinos. O objetivo deste trabalho foi caracterizar a infecção com as cepas isoladas de campo de B. ovis em modelo murino e avaliar a eficiência vacinal da mutante B. ovis ΔabcAB para proteção contra desafio com as cepas isoladas de campo. Foram utilizadas sete cepas isoladas de campo foram capazes de colonizar e provocar lesões no fígado e no baço de camundongos após sete dias pós-infecção. Após triagem, duas cepas foram selecionadas para a melhor caracterização (B. ovis 94 AV and B. ovis 266L). Ambas apresentaram crescimento em placa de cultivo semelhante ao da cepa de referência B. ovis ATCC 25840. A vacinação com a cepa de Brucella ovis ΔabcBA encapsulada com alginato a 1% foi capaz de proteger camundongos desafiados com as cepas isoladas de campo, com os seguintes índices de proteção: 0,751, 1,736 e 2,746, para camundongos desafiados com B. ovis ATCC 25840, B. ovis 94 AV e B. ovis 266 L, respectivamente. Estes resultados demonstraram que as cepas isoladas de campo de B. ovis são capazes de infectar e induzir lesão em camundongos experimentalmente infectados. O uso da cepa ABSTRACT.-Carvalho T.P., Ribeiro N.Q., Mol J.P.S., Costa F.B., Eckstein C., Paula N.F., Paixão T.A. & Santos R.L. 2020. Pathogenic potential of Brucella ovis field isolates with different genotypic profile and protection provided by the vaccine strain B. ovis ΔabcBA against B. ovis field isolates in mice. Pesquisa Veterinária Brasileira 40 (2):88-96. Brucella ovis causes economic and reproductive losses in sheep herds. The goal of this study was to characterize infection with B. ovis field isolates in a murine model, and to evaluate protection induced by the candidate vaccine strain B. ovis ΔabcBA in mice challenged with these field isolates. B. ovis field strains were able to colonize and cause lesions in the liver and spleen of infected mice. After an initial screening, two strains were selected for further characterization (B. ovis 94 AV and B. ovis 266 L). Both strains had in vitro growth kinetics that was similar to that of the reference strain B. ovis ATCC 25840. Vaccination with B. ovis ΔabcBA encapsulated with 1% alginate was protective against the challenge with field strains, with the following protection indexes: 0.751, 1.736, and 2.746, for mice challenged with B. ovis ATCC25840, B. ovis 94 AV, and B. ovis 266 L, respectively. In conclusion, these results demonstrated that B. ovis field strains were capable of infecting and inducing lesions in experimentally infected mice. The attenuated vaccine strain B. ovis ΔabcBA induced protection in mice challenged with different B. ovis field isolates, resulting in higher protection indexes against more pathogenic strains. INDEX TERMS: Pathogeny, Brucella ovis, isolates, genotypic profile, protection, vaccine strain ΔabcBA, mice, immuni...

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Brucella ovis lacking a species-specific putative ATP-binding cassette transporter is attenuated but immunogenic in rams

Cited by 17 publications

References 27 publications

Evaluation in mice of Brucella ovis attenuated mutants for use as live vaccines against B. ovis infection

Evaluation in mice of Brucella ovis attenuated mutants for use as live vaccines against B. ovis infection

Protection Provided by an Encapsulated Live Attenuated ΔabcBAStrain of Brucella ovis against Experimental Challenge in a Murine Model

Pathogenic potential of Brucella ovis field isolates with different genotypic profile and protection provided by the vaccine strain B. ovis ΔabcBA against B. ovis field isolates in mice

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