A Leptospira borgpetersenii Serovar Hardjo Vaccine Induces a Th1 Response, Activates NK Cells, and Reduces Renal Colonization

Zuerner, Richard L.; Alt, David P.; Palmer, Mitchell V.; Thacker, Tyler C.; Olsen, Steven C.

doi:10.1128/cvi.00288-10

Cited by 68 publications

(73 citation statements)

References 21 publications

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“…The anti-inflammatory cytokine IL-10 and IL-4 was also up regulated in rI-LipL21/rLipL21 immunized mice, demonstrating stimulated activation of B-cell and Tcell. IFN-γ production was related to protection in cattle vaccinated with monovalent serovar Hardjo vaccines [30]. In the present study, however, significantly increased IFN-γ mRNA levels ( Figure 5E) were found in mice immunized with rLiPL21 and rI-LipL21, demonstrating the indication of protective immune response for these proteins.…”

Section: Discussioncontrasting

confidence: 56%

Protective immunity of recombinant LipL21 and I-LipL21 against Leptospira interrogans serovar Autumnalis N2 infection

Anita

Premlatha

Veerapandian

et al. 2018

J Infect Dev Ctries

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Introduction: Leptospirosis is a zoonotic disease caused by the spirochete of genus Leptospira with widespread distribution in tropical, subtropical and temperate zones. Leptospirosis is often confused with other febrile illnesses including jaundice, dengue, and malaria. Generally, the disease is often underdiagnosed or misdiagnosed. Though leptospirosis is curable with antibiotic treatment, the laboratory diagnosis of the disease is specialized and open to interpretation with multiple kits available to detect the different serological markers of Leptospira. Moreover, when leptospirosis is misdiagnosed, the disease can lead to multi-organ failure and may have fatal effects. There is a need for strategies to develop vaccines and prevent leptospirosis. In the present study, the immunogenic potential of leptospiral recombinant protein LipL21 (rLipL21) and its truncated form I-LipL21 (rI-LipL21) was evaluated. Methodology: The recombinant proteins were established in cyclophosphamide treated BALB/c mice model infected with L. interrogans serovar Autumnalis strain N2.Results: The vaccination study showed 66% and 83% survivability among mice immunized with rLipL21 and rI-LipL21 respectively and postchallenge with leptospiral strain N2 compared to control groups that showed 100% lethality. Additionally, a significant increase in antibody levels and cytokine levels (TNF-, IFN-γ and IL-10) was observed evidencing a marked stimulation of both humoral and cell-mediated immune response in mice immunized with rLipL21/rI-LipL21 compared to whole cell leptospiral lysate (WCL). Conclusions: This study evidenced protective immunization against leptospirosis with rLipL21 and rI-LipL21 recombinant proteins and are potential candidates for the development of leptospiral vaccine.

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Section: Discussioncontrasting

confidence: 56%

Protective immunity of recombinant LipL21 and I-LipL21 against Leptospira interrogans serovar Autumnalis N2 infection

Anita

Premlatha

Veerapandian

et al. 2018

J Infect Dev Ctries

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“…Therefore, not only humoral immunity but also cell-mediated immunity seems to play an important role in protection against leptospirosis (28,35). Some studies have shown that cattle vaccines stimulating cellular immune responses are able to provide protection, while those stimulating high antibody titers are not (38). This phenomenon is not well understood for other species.…”

Section: Discussionmentioning

confidence: 99%

Protection against Lethal Leptospirosis after Vaccination with LipL32 Coupled or Coadministered with the B Subunit of Escherichia coli Heat-Labile Enterotoxin

Grassmann

Félix

Santos

et al. 2012

Clin. Vaccine Immunol.

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ABSTRACTLeptospirosis, a worldwide zoonosis, lacks an effective, safe, and cross-protective vaccine. LipL32, the most abundant, immunogenic, and conserved surface lipoprotein present in all pathogenic species ofLeptospira, is a promising antigen candidate for a recombinant vaccine. However, several studies have reported a lack of protection when this protein is used as a subunit vaccine. In an attempt to enhance the immune response, we used LipL32 coupled to or coadministered with the B subunit of theEscherichia coliheat-labile enterotoxin (LTB) in a hamster model of leptospirosis. After homologous challenge with 5× the 50% lethal dose (LD50) ofLeptospira interrogans, animals vaccinated with LipL32 coadministered with LTB and LTB::LipL32 had significantly higher survival rates (P< 0.05) than animals from the control group. This is the first report of a protective immune response afforded by a subunit vaccine using LipL32 and represents an important contribution toward the development of improved leptospirosis vaccines.

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“…Whole-cell sonicates (WCSs) and proteinase K-digested WCSs (PKWCSs) from M. bovis 95-1315 were used at 10 mg/ml (44). WCSs from L. borgpetersenii serovar Hardjo, Brucella ovis, and Treponema phagedenis were used at 10 mg/ml as negative-control Ags (45,46). The specific protein and nonprotein Ags used in this study were .98% pure and were tested for endotoxin levels using the ToxinSensor Chromogenic LAL Endotoxin Assay Kit (GenScript).…”

Section: Abs and Reagentsmentioning

confidence: 99%

Specific Recognition of Mycobacterial Protein and Peptide Antigens by γδ T Cell Subsets following Infection with VirulentMycobacterium bovis

McGill

Sacco

Baldwin

et al. 2014

The Journal of Immunology

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Promoting effective immunity to Mycobacterium bovis infection is a challenge that is of interest to the fields of human and animal medicine alike. We report that γδ T cells from virulent M. bovis–infected cattle respond specifically and directly to complex, protein, and nonprotein mycobacterial Ags. Importantly, to our knowledge, we demonstrate for the first time that bovine γδ T cells specifically recognize peptide Ags derived from the mycobacterial protein complex ESAT6:CFP10 and that this recognition requires direct contact with APCs and signaling through the T cell Ag receptor but is independent of MHC class I or II. Furthermore, we show that M. bovis infection in cattle induces robust IL-17A protein responses. Interestingly, in contrast to results from mice, bovine CD4 T cells, and not γδ T cells, are the predominant source of this critical proinflammatory mediator. Bovine γδ T cells are divided into subsets based upon their expression of Workshop Cluster 1 (WC1), and we demonstrate that the M. bovis–specific γδ T cell response is composed of a heterogeneous mix of WC1-expressing populations, with the serologically defined WC1.1+ and WC1.2+ subsets responding in vitro to mycobacterial Ags and accumulating in the lesions of M. bovis–infected animals. The results described in this article enhance our understanding of γδ T cell biology and, because virulent M. bovis infection of cattle represents an excellent model of tuberculosis in humans, contribute to our overall understanding of the role of γδ T cells in the mycobacterial-specific immune response.

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A Leptospira borgpetersenii Serovar Hardjo Vaccine Induces a Th1 Response, Activates NK Cells, and Reduces Renal Colonization

Cited by 68 publications

References 21 publications

Protective immunity of recombinant LipL21 and I-LipL21 against Leptospira interrogans serovar Autumnalis N2 infection

Protective immunity of recombinant LipL21 and I-LipL21 against Leptospira interrogans serovar Autumnalis N2 infection

Protection against Lethal Leptospirosis after Vaccination with LipL32 Coupled or Coadministered with the B Subunit of Escherichia coli Heat-Labile Enterotoxin

Specific Recognition of Mycobacterial Protein and Peptide Antigens by γδ T Cell Subsets following Infection with VirulentMycobacterium bovis

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