Vaccination with a preparation based on recombinant cysteine peptidases and canine IL-12 does not protect dogs from infection with Leishmania infantum

Poot, Jacqueline; Spreeuwenberg, K.; Sanderson, Sanya J.; Schijns, Virgil E. C. J.; Mottram, Jeremy C.; Coombs, Graham H.; Vermeulen, A.N.

doi:10.1016/j.vaccine.2005.12.039

Cited by 33 publications

(21 citation statements)

References 44 publications

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“…13,24,26,27 In fact, most infection protocols in vaccination or treatment studies appear to be designed to overcome the natural resistance of many dogs and produce full-blown disease in a short time span by delivering a massive dose of parasites by the unnatural route of IV injection. 6,[14][15][16][17] Previous studies showed that experimental IV infection was more likely to lead to overt disease than intradermal inoculation, which typically led to subclinical infection. 11,12,28 Our finding of small liver granulomas, an indication of an active cell mediated immune response, in the intradermally infected dogs is consistent with what was observed in resistant dogs naturally infected in endemic areas.…”

Section: Discussionmentioning

confidence: 99%

“…6,7,9 Studies have used numbers of parasites that ranged from a few thousand to several million, delivered by the intradermal [10][11][12][13] or intravenous routes. 6,[14][15][16][17] Some of these inoculations included an extract of Lutzomyia longipalpis salivary glands in an unsuccessful attempt to increase parasite pathogenicity. 10,11 Notably, only on a few occasions were metacyclic promastigotes included in the inocula.…”

Section: Introductionmentioning

confidence: 99%

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Clinical, Parasitologic, and Immunologic Evolution in Dogs Experimentally Infected with Sand Fly-Derived Leishmania chagasi Promastigotes

Travi¹,

Osorio²,

Saldarriaga³

et al. 2009

The American Journal of Tropical Medicine and Hygiene

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Abstract. Experimental infection of dogs with Leishmania infantum has yielded heterogeneous clinical, parasitologic, and immunologic results. We studied dogs infected with 10 5 or 10 4 sand fly-derived promastigotes delivered by the intradermal (ID) or intravenous (IV) routes. Total mortality over 1 year post-infection reached 23.8%. The mortality and proportion of sustained polysymptomatic dogs was highest in the IV-10 5 group. The early appearance of polysymptoms was associated with an increased risk of progression to death. Dissemination of the parasite to lymph nodes was faster, and the subsequent infectivity to sand flies higher, in the IV compared with ID-infected dogs. Parasite-specific IgG1 or IgG2 production was similar among the groups, but higher interferon-γ (IFN-γ) and interleukin-10 (IL-10) expression was associated with polysymptomatic dogs. On the basis of the data obtained from this study, a sample size analysis using different endpoints for future vaccine trials is described.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Clinical, Parasitologic, and Immunologic Evolution in Dogs Experimentally Infected with Sand Fly-Derived Leishmania chagasi Promastigotes

Travi¹,

Osorio²,

Saldarriaga³

et al. 2009

The American Journal of Tropical Medicine and Hygiene

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“…While PBMC from naturally infected polysymptomatic dogs still proliferate in response to SLA, this is minimal and IFN-γ production in response to Leishmania antigen was completely abolished [39]. In the canine model, the expression of IFN-γ from PBMCs correlates with disease resistance/asymptomatic status in non-vaccinated animals [17,40]; further, IFN-γ is observed to increase and correlate with protection in vaccinated dogs [17,22,41]. In humans, IFN-γ has been shown to be a mediator of resistance to the parasites because of its ability to induce killing of the parasite by macrophages; further, IFN-γ levels increase after treatment [42].…”

Section: Discussionmentioning

confidence: 99%

“…To date, only a small number of Leishmania proteins have been investigated in the canine model of visceral leishmaniasis. The fucose-mannose ligand [15], protein Q [16], purified excreted/secreted antigens from L. infantum [17], H1 and HASPB1 [18], TSA-LmsT11-LeIF trifusion protein [19], Leishmania homologue of receptors for activated C kinase (LACK) [20] and cysteine proteinases [21,22] have been used in vaccine trials with variable success in providing protection to dogs against a parasite challenge.…”

Section: Introductionmentioning

confidence: 99%

Immunogenicity of the P-8 amastigote antigen in the experimental model of canine visceral leishmaniasis

Carrillo

Ahmed

Goldsmith-Pestana

et al. 2007

Vaccine

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The P-8 proteoglycolipid complex , an amastigote antigen of L. pifanoi, has been demonstrated to induce protection in mouse models, as well as to induce Tc1/Th1-like cellular responses in American cutaneous leishmaniasis patients. Because the immunization with P-8 PGLC in the murine model does not appear to be genetically restricted, we have studied the reactivity of the P-8 PGLC in L. infantum infected dogs. In this study, it is shown that PBMC from experimentally infected dogs (asymptomatic, oligosymptomatic) significantly proliferated in response to soluble leishmanial antigen (SLA) or the P-8 PGLC. Further, quantification of the gene expression induced by the stimulation with P-8 in asymptomatically infected dogs showed an up-regulation of IFN-γ and TNF-α, which were three to four-fold higher than that induced by soluble Leishmania antigen (SLA). While no measurable induction of IL-10 was observed, low levels of IL-4 mRNA were observed in response to both P-8 and SLA antigens. Thus, our studies establish that P-8 is recognized by infected canines and elicits a potentially curative/protective Th1-like immune response. The identification of Leishmania antigens that elicit appropriate immune responses across different host species (humans, canine) and disease manifestations (cutaneous or visceral) could be an advantage in generating a general vaccine for leishmaniasis.

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“…MON-1 is one of the most prevalent zymodemes in Europe and the Mediterranean basin, in countries such as Greece, France, Spain, Italy, Algeria and Syria, and is also found in Brazil [30-35]. JPCM5 has been shown to be virulent to hamsters (this study) and dogs [36], causing the symptoms of visceral leishmaniasis in both animals. These observations are important as they show that the parasite has maintained its virulence following isolation, cloning and prolonged culture in the laboratory.…”

Section: Discussionmentioning

confidence: 91%

Studies on the CPA cysteine peptidase in the Leishmania infantum genome strain JPCM5

Denise

Poot²,

Jiménez

et al. 2006

BMC Molecular Biol

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Background: Visceral leishmaniasis caused by members of the Leishmania donovani complex is often fatal in the absence of treatment. Research has been hampered by the lack of good laboratory models and tools for genetic manipulation. In this study, we have characterised a L. infantum line (JPCM5) that was isolated from a naturally infected dog and then cloned. We found that JPCM5 has attributes that make it an excellent laboratory model; different stages of the parasite life cycle can be studied in vitro, it is accessible to genetic manipulation and it has retained its virulence. Furthermore, the L. infantum JPCM5 genome has now been fully sequenced.

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Vaccination with a preparation based on recombinant cysteine peptidases and canine IL-12 does not protect dogs from infection with Leishmania infantum

Cited by 33 publications

References 44 publications

Clinical, Parasitologic, and Immunologic Evolution in Dogs Experimentally Infected with Sand Fly-Derived Leishmania chagasi Promastigotes

Clinical, Parasitologic, and Immunologic Evolution in Dogs Experimentally Infected with Sand Fly-Derived Leishmania chagasi Promastigotes

Immunogenicity of the P-8 amastigote antigen in the experimental model of canine visceral leishmaniasis

Studies on the CPA cysteine peptidase in the Leishmania infantum genome strain JPCM5

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