Recombinant Mycobacterium bovis BCG expressing the LipL32 antigen of Leptospira interrogans protects hamsters from challenge

Seixas, Fabiana Kömmling; Silva, Éverton Fagonde da; Hartwig, Daiane Drawanz; Cerqueira, Gustavo M.; Amaral, Marta; Fagundes, Michel Quevedo; Dossa, Robson G.; Dellagostin, Odir A.

doi:10.1016/j.vaccine.2007.10.052

Cited by 89 publications

(64 citation statements)

References 39 publications

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“…Ideally an effective vaccine would induce induce cross-protection against the range of serovars of public health importance. Encorauging data using recombinant proteins and DNA vaccines in different animal models has already been published [13][14][15][16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Characterization of virulence of Leptospira isolates in a hamster model

Silva

Santos

Athanazio

et al. 2008

Vaccine

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Effort has been made to identify protective antigens in order to develop a recombinant vaccine against leptospirosis. Several attempts failed to conclusively demonstrate efficacy of vaccine candidates due to the lack of an appropriate model of lethal leptospirosis. The purposes of our study were: (i) to test the virulence of leptospiral isolates from Brazil, which are representative of important serogroups that cause disease in humans and animals; and (ii) to standardize the lethal dose 50% (LD 50 ) for each of the virulent strains using a hamster (Mesocricetus auratus) model. Five of seven Brazilian isolates induced lethality in a hamster model, with inocula lower than 200 leptospires. Histopathological examination of infected animals showed typical lesions found in both natural and experimental leptospirosis. Results described here demonstrated the potential use of Brazilian isolates as highly virulent strains in challenge experiments using hamster as an appropriate animal model for leptospirosis. Furthermore these strains may be useful in heterologous challenge studies which aim to evaluate cross-protective responses induced by subunit vaccine candidates.

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Section: Introductionmentioning

confidence: 99%

Characterization of virulence of Leptospira isolates in a hamster model

Silva

Santos

Athanazio

et al. 2008

Vaccine

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“…Experiments are currently been conducted to test this hypothesis. If confirmed, other rBCG vaccine candidates that have already been demonstrated to induce protection in animal model experiments (Connell et al, 1993;Buddle et al, 1995;Abomoelak et al, 1999;Demangel et al, 2005;Dennehy et al, 2007;Seixas et al, 2007a) could also be further improved by the use of the new expression system.…”

Section: Resultsmentioning

confidence: 95%

“…This is the first report of evaluation of rBCG stability in hamster. Recombinant BCG expressing LipL32 antigen from L. interrogans has been shown to protect hamsters from a lethal challenge, using a conventional expression system (Seixas et al, 2007a). We are confident that the improved stability provided by the auxotrophic complementation system will be able to further enhance the immune response elicited by rBCG expressing LipL32, conferring a higher protection level.…”

Section: Resultsmentioning

confidence: 98%

“…The extraordinary adjuvant properties of mycobacteria make them an attractive vector for the development of recombinant vaccines (Stover et al, 1991;Bastos et al, 2009). Indeed, antigens from bacteria, parasites, and viruses have been expressed in BCG and tested for this purpose (Bastos et al, 2002;Varaldo et al, 2004;Seixas et al, 2007a;da Silva Ramos et al, 2008). In addition, it has been shown that heterologous antigens expressed by recombinant BCG (rBCG) can elicit both cellular and humoral immune responses (Dennehy & Williamson, 2005).…”

Section: Introductionmentioning

confidence: 99%

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Stable expression of Leptospira interrogans antigens in auxotrophic Mycobacterium bovis BCG

et al. 2010

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Mycobacterium bovis BCG has been proposed as an effective live vector for multivalent vaccines. The development of mycobacterial genetic systems to express foreign antigens and the adjuvanticity of BCG are the basis for the potential use of this attenuated mycobacterium as a recombinant vaccine vector. Stable plasmid vectors without antibiotic resistance markers are needed for heterologous antigen expression in BCG. Our group recently described the construction of a BCG expression system using auxotrophic complementation as a selectable marker. In this work, LipL32 and LigAni antigens of Leptospira interrogans were cloned and expressed in M. bovis BCG Pasteur and in the auxotrophic M. bovis BCG ΔleuD strains under the control of the M. leprae 18kDa promoter. Stability of the plasmids during in vitro growth and after inoculation of the recombinant BCG strains in hamsters was compared. The auxotrophic complementation system was highly stable, even during in vivo growth, as the selective pressure was maintained, whereas the conventional vector was unstable in the absence of selective pressure. These results confirm the usefulness of the new expression system, which represents a huge improvement over previously described expression systems for the development of BCG into an effective vaccine vector.

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“…A partir dessas evidências experimentais, várias outras proteínas de leptospiras têm sido testadas como candidatos vacinais. LipL32, a proteína imunodominante de leptospiras, já foi testada na forma de vacina de DNA (BRANGER et al, 2005), BCG como veículo vivo expressando LipL32 (SEIXAS et al, 2007), LipL32 coadministrada com a subunidade B da toxina LT de E. coli (GRASSMANN et al, 2012) e fusionada a LigANI (LUCAS et al, 2011 (FAISAL et al, 2008;FAISAL et al, 2009;PALANIAPPAN et al, 2006;SILVA et al, 2007;YAN et al, 2009 (HANAHAN, 1983). Foram utilizados 5µL do produto de ligação para 50 µL de bactérias competentes, que foram incubadas por 30 minutos em banho de gelo e, em seguida, submetidas a um choque térmico, por 2 minutos a 42 ºC.…”

Section: Desenvolvimento De Vacinasunclassified

Avaliação e caracterização de candidatos vacinais voltados para o controle da leptospirose.

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Recombinant Mycobacterium bovis BCG expressing the LipL32 antigen of Leptospira interrogans protects hamsters from challenge

Cited by 89 publications

References 39 publications

Characterization of virulence of Leptospira isolates in a hamster model

Characterization of virulence of Leptospira isolates in a hamster model

Stable expression of Leptospira interrogans antigens in auxotrophic Mycobacterium bovis BCG

Avaliação e caracterização de candidatos vacinais voltados para o controle da leptospirose.

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