Leptospirosis Vaccine: Search for Subunit Candidates

Félix, Samuel Rodrigues; Silva, É.F.; Jouglard, Sandra Denise Dorneles; Hartmann, D.M.; Grassmann, André Alex; Dellagostin, Odir A.

doi:10.1016/j.provac.2009.07.020

Cited by 4 publications

(3 citation statements)

References 26 publications

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“…Our results show high survival rates for animals receiving recombinant LipL32 coadministered with or coupled to an LTB adjuvant, representing significant protection compared to that for any of the control groups (log-rank test). The level of significance of the results would be even higher if there were no surviving animals in the control groups; however, survival of a few animals from negative-control groups challenged with L. interrogans strain L1-130 is not uncommon (2,(10)(11)(12)30).…”

Section: Discussionmentioning

confidence: 96%

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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Section: Discussionmentioning

confidence: 96%

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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“…In recent years, many potential vaccine candidates have been tested in animal models, and several different approaches, including those employing subunit, DNA, adenovirus, and Mycobacterium bovis BCG constructs, have been used (2,5,6,12,13,15,19,24,26,27). Most of these studies identified their protein targets by screening for antigenicity through the use of sera from patients with leptospirosis (14) and/or proteins with predicted surface exposure (10).…”

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confidence: 99%

Subunit Approach to Evaluation of the Immune Protective Potential of Leptospiral Antigens

Félix

Hartwig

Argondizzo

et al. 2011

Clin Vaccine Immunol

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Leptospirosis is the most widespread zoonosis in the world. Current vaccines are based on whole-cell preparations that cause severe side effects and do not induce satisfactory immunity. In light of the leptospiral genome sequences recently made available, several studies aimed at identification of protective recombinant immunogens have been performed; however, few such immunogens have been identified. The aim of this study was to evaluate 27 recombinant antigens to determine their potential to induce an immune response protective against leptospirosis in the hamster model. Experiments were conducted with groups of female hamsters immunized with individual antigen preparations. Hamsters were then challenged with a lethal dose of Leptospira interrogans. Thirteen antigens induced protective immune responses; however, only recombinant proteins LIC10325 and LIC13059 induced significant protection against mortality. These results have important implications for the development of an efficacious recombinant subunit vaccine against leptospirosis.

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“…Furthermore, we describe a thorough standardization of the LD50 and pathological inflictions. In 2008, Silva and others 6 published a similar study using different strains that enabled the execution of several assays, mainly vaccine trials 24 and pathogenicity studies. 25 The current work, associated with the complete genome sequence of L. borgpetersenii serovar Hardjo, 26 should allow for the development of studies related to heterologous vaccine trials as well as compare pathogenesis with virulence studies.…”

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confidence: 99%

Highly Virulent Leptospira borgpetersenii Strain Characterized in the Hamster Model

Diniz

Félix²,

Bonel-Raposo³

et al. 2011

The American Society of Tropical Medicine and Hygiene

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A recent study by our group reported the isolation and partial serological and molecular characterization of four Leptospira borgpetersenii serogroup Ballum strains. Here, we reproduced experimental leptospirosis in golden Syrian hamsters (Mesocricetus auratus) and carried out standardization of lethal dose 50% (LD50) of one of these strains (4E). Clinical disease features and histopathologic analyses of tissue lesions were also observed. As results, strain 4E induced lethality in the hamster model with inocula lower than 10 leptospires, and histopathological examination of animals showed typical lesions found in severe leptospirosis. Gross pathological findings were peculiar; animals that died early had more chance of presenting severe jaundice and less chance of presenting pulmonary hemorrhages (P < 0.01). L. borgpetersenii serogroup Ballum has had a considerable growth in human leptospirosis cases in recent years. This strain has now been thoroughly characterized and can be used in more studies, especially evaluations of vaccine candidates.

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Leptospirosis Vaccine: Search for Subunit Candidates

Cited by 4 publications

References 26 publications

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

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

Subunit Approach to Evaluation of the Immune Protective Potential of Leptospiral Antigens

Highly Virulent Leptospira borgpetersenii Strain Characterized in the Hamster Model

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