Recombinant BCG strains expressing chimeric proteins derived from Leptospira protect hamsters against leptospirosis

Oliveira, Thaís Larré; Rizzi, Caroline; Cunha, C. E.; Dorneles, Jessica; Neto, Amilton Clair Pinto Seixas; Amaral, Marta; Hartwig, Daiane Drawanz; Dellagostin, Odir Antônio

doi:10.1016/j.vaccine.2018.12.050

Cited by 27 publications

(25 citation statements)

References 28 publications

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“…Unlike previous reports [9,48,49], our separate studies in hamsters showed that 20%, but not 10%, weight loss was correlated with dead outcome (Supplementary Figure S5). The hamsters with 10% weight loss could later gain their weight and finally survived up to the end of the experiment.…”

Section: Discussioncontrasting

confidence: 99%

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Reduced Renal Colonization and Enhanced Protection by Leptospiral Factor H Binding Proteins as a Multisubunit Vaccine against Leptospirosis in Hamsters

et al. 2019

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Subunit vaccines conferring complete protection against leptospirosis are not currently available. The interactions of factor H binding proteins (FHBPs) on pathogenic leptospires and host factor H are crucial for immune evasion by inhibition of complement-mediated killing. The inhibition of these interactions may be a potential strategy to clear leptospires in the host. This study aimed to evaluate a multisubunit vaccine composed of four known leptospiral FHBPs: LigA domain 7–13 (LigAc), LenA, LcpA, and Lsa23, for its protective efficacy in hamsters. The mono and multisubunit vaccines formulated with LMQ adjuvant, a combination of neutral liposome, monophosphoryl lipid A, and Quillaja saponaria fraction 21, induced high and comparable specific antibody (IgG) production against individual antigens. Hamsters immunized with the multisubunit vaccine showed 60% survival following the challenge by 20 LD50 of Leptospira interrogans serovar Pomona. No significant difference in survival rate and pathological findings of target organs was observed after vaccinations with multisubunit or mono-LigAc vaccines. However, the multisubunit vaccine significantly reduced leptospiral burden in surviving hamsters in comparison with the monosubunit vaccines. Therefore, the multisubunit vaccine conferred partial protection and reduced renal colonization against virulence Leptospira infection in hamsters. Our multisubunit formulation could represent a promising vaccine against leptospirosis.

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Section: Discussioncontrasting

confidence: 99%

“…Further investigations using different combinations of these subunit vaccines including all FHBPs, except LigAc, are required to determine the crucial components. Chimeric vaccines containing fusion of protective FHBPs will be a promising strategy to deliver the vaccine antigens as previously reported [49,52,53].…”

Section: Discussionmentioning

confidence: 99%

Reduced Renal Colonization and Enhanced Protection by Leptospiral Factor H Binding Proteins as a Multisubunit Vaccine against Leptospirosis in Hamsters

et al. 2019

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“…(6) LemA is present in different serovars and significantly protects hamsters when administered as subunit (50.0-87.5%), DNA (62.5%), or when vectored by rBCG under the control of different promoters (80-100%). (5,6,22) Thus, the vaccine potential of this protein deserves to be better explored. In this study, vaccination with the rLemA-based DNA vaccine (pTARGET/ lemA) protected 50% of the immunised hamsters, which was not significantly different from the results for the negative control (0% protection).…”

Section: Discussionmentioning

confidence: 99%

DNA nanovaccines prepared using LemA antigen protect Golden Syrian hamsters against Leptospira lethal infection

Oliveira

Bacelo

Forster

et al. 2020

Mem. Inst. Oswaldo Cruz

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BACKGROUND Nanoparticles (NPs) are viable candidates as carriers of exogenous materials into cells via transfection and can be used in the DNA vaccination strategy against leptospirosis. OBJECTIVES We evaluated the efficiency of halloysite clay nanotubes (HNTs) and amine-functionalised multi-walled carbon nanotubes (NH 2-MWCNTs) in facilitating recombinant LemA antigen (rLemA) expression and protecting Golden Syrian hamsters (Mesocricetus auratus) against Leptospira interrogans lethal infection. METHODS An indirect immunofluorescent technique was used to investigate the potency of HNTs and NH 2-MWCNTs in enhancing the transfection and expression efficiency of the DNA vaccine in Chinese hamster ovary (CHO) cells. Hamsters were immunised with two doses of vaccines HNT-pTARGET/lemA, NH 2-MWCNTs-pTARGET/lemA, pTARGET/lemA, and empty pTARGET (control), and the efficacy was determined in terms of humoral immune response and protection against a lethal challenge. FINDINGS rLemA DNA vaccines carried by NPs were able to transfect CHO cells effectively, inducing IgG immune response in hamsters (p < 0.05), and did not exhibit cytotoxic effects. Furthermore, 83.3% of the hamsters immunised with NH 2-MWCNTs-pTARGET/lemA were protected against the lethal challenge (p < 0.01), and 66.7% of hamsters immunised with HNT-pTARGET/ lemA survived (p < 0.05). MAIN CONCLUSIONS NH 2-MWCNTs and HNTs can act as antigen carriers for mammalian cells and are suitable for DNA nanovaccine delivery.

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“…Although inducible promoters have their extensive use in molecular biology, constitutive expression systems such as hsp60 promoter also have significant applicability. Indeed, hsp60 promoter, because of its generally constitutive expression at 37˚C, has been used in several studies [21][22][23][24], suggesting strongly the utility of our designed plasmids with this promoter.…”

Section: Plos Onementioning

confidence: 95%

Construction of E. coli—Mycobacterium shuttle vectors with a variety of expression systems and polypeptide tags for gene expression in mycobacteria

2020

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Cloning and expression of a desired gene is indispensable in molecular biology studies. Expression vectors, in this regard, should offer much needed flexibility and choice of cloning strategies for both in vivo and in vitro protein expression experiments. Furthermore, availability of option to choose from various reporter tags allows one to be flexible during designing of an experiment in a more relevant manner. Thus, the need of a versatile expression system cannot be ignored. Although several different expression vectors are available for gene expression in mycobacteria, they lack the required versatility of expression and the inclusion of reporter tags. We here present the construction of a set of nine E. coli-Mycobacterium shuttle plasmids, which offer a combination of three mycobacterial promoter systems (heat shock inducible-hsp60, tetracycline-, and acetamide-inducible) along with three polypeptide tags (Green Fluorescent Protein (GFP), Glutathione S-transferase (GST) and hexahistidine tag). These vectors offer the cloning of a target gene in all the nine given vectors in parallel, thus allowing the generation of recombinant plasmids that will express the target gene from different promoters with different tags. Here, while the hexa-histidine and GST tags can be used for protein purification and pull-down experiments, the GFP-tag can be used for protein localization within the cell. Additionally, the vectors also offer the choice of positioning of the reporter tag either at the N-terminus or at the C-terminus of the expressed protein, which is achieved by cloning of the gene at any of the two blunt-end restriction enzyme sites available in the vector. We believe that these plasmids will be extremely useful in the gene expression studies in mycobacteria by offering the choices of promoters and reporters. Our work also paves the way to developing more such plasmids with other tags and promoters that may find use in mycobacterial biology.

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Recombinant BCG strains expressing chimeric proteins derived from Leptospira protect hamsters against leptospirosis

Cited by 27 publications

References 28 publications

Reduced Renal Colonization and Enhanced Protection by Leptospiral Factor H Binding Proteins as a Multisubunit Vaccine against Leptospirosis in Hamsters

Reduced Renal Colonization and Enhanced Protection by Leptospiral Factor H Binding Proteins as a Multisubunit Vaccine against Leptospirosis in Hamsters

DNA nanovaccines prepared using LemA antigen protect Golden Syrian hamsters against Leptospira lethal infection

Construction of E. coli—Mycobacterium shuttle vectors with a variety of expression systems and polypeptide tags for gene expression in mycobacteria

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