Intranasal Vaccination against Cutaneous Leishmaniasis with a Particulated Leishmanial Antigen or DNA Encoding LACK

Pinto, Eduardo Costa; Pinheiro, Roberta Olmo; Rayol, Alice; Larraga, Vicente; Rossi-Bergmann, Bartira

doi:10.1128/iai.72.8.4521-4527.2004

Cited by 54 publications

(55 citation statements)

References 39 publications

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“…There are different examples of how intra-nasal vaccination has led to protective immune responses against other non-mucosal, penetrative pathogens, including Plasmodium and Leishmania (Arakawa et al 2003(Arakawa et al , 2005Hirunpetcharat et al 1998 ;Pinto et al 2004). In addition, intra-nasal immunization with Toxoplasma gondii TgSAG1 and non-toxic heatlabile enterotoxins protected mice against challenge infection against T. gondii (Bonenfant et al 2001), and recently Igarashi et al (2007) showed that intranasal immunization in Balb/c mice with recombinant TgROP2, TgGRA5 and TgGRA7 applied with cholera toxin induced partial protection against tissue cyst formation after oral infection with Toxoplasma tissue cysts.…”

Section: Discussionmentioning

confidence: 99%

Intraperitoneal and intra-nasal vaccination of mice with three distinct recombinantNeospora caninumantigens results in differential effects with regard to protection against experimental challenge withNeospora caninumtachyzoites

et al. 2009

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S U M M A R YRecombinant NcPDI(recNcPDI), NcROP2(recNcROP2), and NcMAG1(recNcMAG1) were expressed in Escherichia coli and purified, and evaluated as potential vaccine candidates by employing the C57Bl/6 mouse cerebral infection model. Intraperitoneal application of these proteins suspended in saponin adjuvants lead to protection against disease in 50 % and 70 % of mice vaccinated with recNcMAG1 and recNcROP2, respectively, while only 20 % of mice vaccinated with recNcPDI remained without clinical signs. In contrast, a 90 % protection rate was achieved following intra-nasal vaccination with recNcPDI emulsified in cholera toxin. Only 1 mouse vaccinated intra-nasally with recNcMAG1 survived the challenge infection, and protection achieved with intra-nasally applied recNcROP2 was at 60 %. Determination of cerebral parasite burdens by real-time PCR showed that these were significantly reduced only in recNcROP2-vaccinated animals (following intraperitoneal and intra-nasal application) and in recNcPDI-vaccinated mice (intra-nasal application only). Quantification of viable tachyzoites in brain tissue of intra-nasally vaccinated mice showed that immunization with recNcPDI resulted in significantly decreased numbers of live parasites. These data show that, besides the nature of the antigen, the protective effect of vaccination also depends largely on the route of antigen delivery. In the case of recNcPDI, the intra-nasal route provides a platform to generate a highly protective immune response.

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Section: Discussionmentioning

confidence: 99%

Intraperitoneal and intra-nasal vaccination of mice with three distinct recombinantNeospora caninumantigens results in differential effects with regard to protection against experimental challenge withNeospora caninumtachyzoites

et al. 2009

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“…These findings suggest that L. amazonensis parasites take advantage of the host IFN-γ response for their intracellular survival. However, in other circumstances such as following protective mucosal vaccination with parasite antigens, the systemic production of IFN-γ may be effective (Pinto et al 2004, Pinheiro et al 2006. Since the role of IFN-γ during L. amazonensis infection is controversial, we evaluated the course of lesion growth induced by L. amazonensis in IFN-γ KO mice.…”

Section: Discussionmentioning

confidence: 99%

Interferon-gamma is required for the late but not early control of Leishmania amazonensis infection in C57Bl/6 mice

Pinheiro

Rossi-Bergmann

2007

Mem. Inst. Oswaldo Cruz

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The critical role of interferon-gamma (IFN-γ) in the resistance of C57Bl/6 mice to Leishmania major is widely established but its role in the relative resistance of these animals to L. amazonensis infection is still not clear. In this work we use C57Bl/6 mice congenitally deficient in the IFN-γ gene (IFN-γ KO) Leishmaniasis is a complex of diseases caused by the obligate intracellular protozoan parasites of the genus Leishmania. The various clinical forms of human leishmaniasis have been partially reproduced in different strains of mice. For example, C57Bl/6 mice infected with L. major develop cutaneous lesions that spontaneously heal, whereas BALB/c mice harbor non-healing cutaneous lesions. Such experimental models have earlier allowed definition of some of the immunological factors involved in resistance and susceptibility to L. major infection (Reiner & Locksley 1995). During L. major infection of mice, a polarized differentiation of Th1/Th2 CD4 + T cells occurs in resistant and susceptible mice and the Th1 cytokine interferon-γ (IFN-γ) plays an essential role in controlling parasite growth and disease progression (Scott 1991, Liew et al. 1997. Evidence for the critical role for IFN-γ in the control of L. major infection comes from the demonstration that IFN-γ knockout (KO) mice fail to cure infection (Wang et al. 1994).In contrast to L. major, the immunological mechanisms determining susceptibility and resistance to L. amazonensis have been less studied. This is of relevance since the pathogenesis caused by L. amazonensis in humans follows a pattern different from that described for L. major and has been associated not only with localized cutaneous lesions but also with diffuse cutaneous leishmaniasis and more rarely, fatal visceral leishmaniasis (Convit et al. 1993, Almeida et al. 1996. Notably, in IFN-γ production by CD8 + T cells has been associated with immunoregulatory responses induced by leishmanial antigens that elicit significant protection against L. amazonensis (Champsi & McMahon-Pratt 1988, Soong et al. 1997) and an overproduction of IFN-γ seems necessary for development of a resistant phenotype (Afonso & Scott 1993). The protective role of IFN-γ in L. amazonensis infection is further questioned in a more recent report showing that IFN-γ promotes the replication of L. amazonensis amastigotes in macrophages, as opposed to its inhibitory effect on L. major infected macrophages (Qi et al. 2004). In vivo, adoptive transfer of naïve splenocytes devoid of CD4 + CD25 + Treg cells into RAG1-/-mice before infection markedly exacerbated disease progression, and this effect was associated with a marked production of IFN-γ by the effector T cells (Ji et al. 2005). Since the role of IFN-γ during L. amazonensis infection is not a resolved issue, in the present work we proposed to evaluate the course of L. amazonensis infection in IFN-γ KO mice. MATERIALS AND METHODSMice -C57Bl/6-background IFN-γ KO mice were a kind gift of Dr Leda Quércia Vieira (Gnotobiology Laboratory, Federal University of Minas Gerais,...

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“…Several Leishmania proteins have been identified, and the most comprehensively studied antigens include glycoprotein 63 (gp63) (Xu et al 1995;Bhowmick et al 2008), glycoprotein 46 (gp46) or parasite surface antigen 2 (PSA-2) (McMahon-Pratt et al 1992, 1993, Leishmania homologue of receptors for activated C kinase (LACK) (Coelho et al 2003;Pinto et al 2004), and focused mannose ligand (FML) (Palatnik de Sousa et al 1994;). …”

Section: New Perspectives For Applications Of Proteoliposomesmentioning

confidence: 99%

Proteoliposomes in nanobiotechnology

et al. 2012

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Proteoliposomes are systems that mimic lipid membranes (liposomes) to which a protein has been incorporated or inserted. During the last decade, these systems have gained prominence as tools for biophysical studies on lipid-protein interactions as well as for their biotechnological applications. Proteoliposomes have a major advantage when compared with natural membrane systems, since they can be obtained with a smaller number of lipidic (and protein) components, facilitating the design and interpretation of certain experiments. However, they have the disadvantage of requiring methodological standardization for incorporation of each specific protein, and the need to verify that the reconstitution procedure has yielded the correct orientation of the protein in the proteoliposome system with recovery of its functional activity. In this review, we chose two proteins under study in our laboratory to exemplify the steps necessary for the standardization of the reconstitution of membrane proteins in liposome systems: (1) alkaline phosphatase, a protein with a glycosylphosphatidylinositol anchor, and (2) Na,K-ATPase, an integral membrane protein. In these examples, we focus on the production of the specific proteoliposomes, as well as on their biochemical and biophysical characterization, with emphasis on studies of lipid-protein interactions. We conclude the chapter by highlighting current prospects of this technology for biotechnological applications, including the construction of nanosensors and of a multiprotein nanovesicular biomimetic to study the processes of initiation of skeletal mineralization.

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Intranasal Vaccination against Cutaneous Leishmaniasis with a Particulated Leishmanial Antigen or DNA Encoding LACK

Cited by 54 publications

References 39 publications

Intraperitoneal and intra-nasal vaccination of mice with three distinct recombinantNeospora caninumantigens results in differential effects with regard to protection against experimental challenge withNeospora caninumtachyzoites

Intraperitoneal and intra-nasal vaccination of mice with three distinct recombinantNeospora caninumantigens results in differential effects with regard to protection against experimental challenge withNeospora caninumtachyzoites

Interferon-gamma is required for the late but not early control of Leishmania amazonensis infection in C57Bl/6 mice

Proteoliposomes in nanobiotechnology

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