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Wim Jonckheere - One of the best experts on this subject based on the ideXlab platform.
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the Salivary Protein repertoire of the polyphagous spider mite tetranychus urticae a quest for effectors
Molecular & Cellular Proteomics, 2016Co-Authors: Wim Jonckheere, Wannes Dermauw, Vladimir Zhurov, Nicky Wybouw, Jan Van Den Bulcke, Carlos A Villarroel, Robert Greenhalgh, Mike Grbic, Rob C SchuurinkAbstract:The two-spotted spider mite Tetranychus urticae is an extremely polyphagous crop pest. Alongside an unparalleled detoxification potential for plant secondary metabolites, it has recently been shown that spider mites can attenuate or even suppress plant defenses. Salivary constituents, notably effectors, have been proposed to play an important role in manipulating plant defenses and might determine the outcome of plant-mite interactions. Here, the proteomic composition of saliva from T. urticae lines adapted to various host plants—bean, maize, soy, and tomato—was analyzed using a custom-developed feeding assay coupled with nano-LC tandem mass spectrometry. About 90 putative T. urticae Salivary Proteins were identified. Many are of unknown function, and in numerous cases belonging to multimembered gene families. RNAseq expression analysis revealed that many genes coding for these Salivary Proteins were highly expressed in the proterosoma, the mite body region that includes the Salivary glands. A subset of genes encoding putative Salivary Proteins was selected for whole-mount in situ hybridization, and were found to be expressed in the anterior and dorsal podocephalic glands. Strikingly, host plant dependent expression was evident for putative Salivary Proteins, and was further studied in detail by micro-array based genome-wide expression profiling. This meta-analysis revealed for the first time the Salivary Protein repertoire of a phytophagous chelicerate. The availability of this Salivary proteome will assist in unraveling the molecular interface between phytophagous mites and their host plants, and may ultimately facilitate the development of mite-resistant crops. Furthermore, the technique used in this study is a time- and resource-efficient method to examine the Salivary Protein composition of other small arthropods for which saliva or Salivary glands cannot be isolated easily.
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The Salivary Protein Repertoire of the Polyphagous Spider Mite Tetranychus urticae: A Quest for Effectors *
Molecular & cellular proteomics : MCP, 2016Co-Authors: Wim Jonckheere, Wannes Dermauw, Vladimir Zhurov, Nicky Wybouw, Jan Van Den Bulcke, Carlos A Villarroel, Robert Greenhalgh, Rob C Schuurink, Mike Grbić, Luc TirryAbstract:The two-spotted spider mite Tetranychus urticae is an extremely polyphagous crop pest. Alongside an unparalleled detoxification potential for plant secondary metabolites, it has recently been shown that spider mites can attenuate or even suppress plant defenses. Salivary constituents, notably effectors, have been proposed to play an important role in manipulating plant defenses and might determine the outcome of plant-mite interactions. Here, the proteomic composition of saliva from T. urticae lines adapted to various host plants—bean, maize, soy, and tomato—was analyzed using a custom-developed feeding assay coupled with nano-LC tandem mass spectrometry. About 90 putative T. urticae Salivary Proteins were identified. Many are of unknown function, and in numerous cases belonging to multimembered gene families. RNAseq expression analysis revealed that many genes coding for these Salivary Proteins were highly expressed in the proterosoma, the mite body region that includes the Salivary glands. A subset of genes encoding putative Salivary Proteins was selected for whole-mount in situ hybridization, and were found to be expressed in the anterior and dorsal podocephalic glands. Strikingly, host plant dependent expression was evident for putative Salivary Proteins, and was further studied in detail by micro-array based genome-wide expression profiling. This meta-analysis revealed for the first time the Salivary Protein repertoire of a phytophagous chelicerate. The availability of this Salivary proteome will assist in unraveling the molecular interface between phytophagous mites and their host plants, and may ultimately facilitate the development of mite-resistant crops. Furthermore, the technique used in this study is a time- and resource-efficient method to examine the Salivary Protein composition of other small arthropods for which saliva or Salivary glands cannot be isolated easily.
Fabiano Oliveira - One of the best experts on this subject based on the ideXlab platform.
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dna plasmid coding for phlebotomus sergenti Salivary Protein pssp9 a member of the sp15 family of Proteins protects against leishmania tropica
PLOS Neglected Tropical Diseases, 2019Co-Authors: Fabiano Oliveira, Elham Gholami, Tahereh Taheri, Negar Seyed, Safoora Gharibzadeh, Nasim Gholami, Amir Mizbani, Fatemeh Zali, Sima HabibzadehAbstract:Background The vector-borne disease leishmaniasis is transmitted to humans by infected female sand flies, which transmits Leishmania parasites together with saliva during blood feeding. In Iran, cutaneous leishmaniasis (CL) is caused by Leishmania (L.) major and L. tropica, and their main vectors are Phlebotomus (Ph.) papatasi and Ph. sergenti, respectively. Previous studies have demonstrated that mice immunized with the Salivary gland homogenate (SGH) of Ph. papatasi or subjected to bites from uninfected sand flies are protected against L. major infection. Methods and results In this work we tested the immune response in BALB/c mice to 14 different plasmids coding for the most abundant Salivary Proteins of Ph. sergenti. The plasmid coding for the Salivary Protein PsSP9 induced a DTH response in the presence of a significant increase of IFN-γ expression in draining lymph nodes (dLN) as compared to control plasmid and no detectable PsSP9 antibody response. Animals immunized with whole Ph. sergenti SGH developed only a saliva-specific antibody response and no DTH response. Mice immunized with whole Ph. sergenti saliva and challenged intradermally with L. tropica plus Ph. sergenti SGH in their ears, exhibited no protective effect. In contrast, PsSP9-immunized mice showed protection against L. tropica infection resulting in a reduction in nodule size, disease burden and parasite burden compared to controls. Two months post infection, protection was associated with a significant increase in the ratio of IFN-γ to IL-5 expression in the dLN compared to controls. Conclusion This study demonstrates that while immunity to the whole Ph. sergenti saliva does not induce a protective response against cutaneous leishmaniasis in BALB/c mice, PsSP9, a member of the PpSP15 family of Ph. sergenti Salivary Proteins, provides protection against L. tropica infection. These results suggest that this family of Proteins in Ph. sergenti, Ph. duboscqi and Ph. papatasi may have similar immunogenic and protective properties against different Leishmania species. Indeed, this anti-saliva immunity may act as an adjuvant to accelerate the cell-mediated immune response to co-administered Leishmania antigens, or even cause the activation of infected macrophages to remove parasites more efficiently. These findings highlight the idea of applying arthropod saliva components in vaccination approaches for diseases caused by vector-borne pathogens.
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intradermal immunization of leishmania donovani centrin knock out parasites in combination with Salivary Protein ljm19 from sand fly vector induces a durable protective immune response in hamsters
PLOS Neglected Tropical Diseases, 2016Co-Authors: Jesus G Valenzuela, Jacqueline Araujo Fiuza, Dwann Davenport, Maha Abdeladhim, Claudio Meneses, Fabiano Oliveira, Shaden Kamhawi, Sreenivas Gannavaram, Hira L NakhasiAbstract:BACKGROUND: Visceral leishmaniasis (VL) is a neglected tropical disease and is fatal if untreated. There is no vaccine available against leishmaniasis. The majority of patients with cutaneous leishmaniasis (CL) or VL develop a long-term protective immunity after cure from infection, which indicates that development of an effective vaccine against leishmaniasis is possible. Such protection may also be achieved by immunization with live attenuated parasites that do not cause disease. We have previously reported a protective response in mice, hamsters and dogs with Leishmania donovani centrin gene knock-out parasites (LdCen-/-), a live attenuated parasite with a cell division specific centrin1 gene deletion. In this study we have explored the effects of Salivary Protein LJM19 as an adjuvant and intradermal (ID) route of immunization on the efficacy of LdCen-/- parasites as a vaccine against virulent L. donovani. METHODOLOGY/PRINCIPAL FINDINGS: To explore the potential of a combination of LdCen-/- parasites and Salivary Protein LJM19 as vaccine antigens, LdCen-/- ID immunization followed by ID challenge with virulent L. donovani were performed in hamsters in a 9-month follow up study. We determined parasite burden (serial dilution), antibody production (ELISA) and cytokine expression (qPCR) in these animals. Compared to controls, animals immunized with LdCen-/- + LJM19 induced a strong antibody response, a reduction in spleen and liver parasite burden and a higher expression of pro-inflammatory cytokines after immunization and one month post-challenge. Additionally, a low parasite load in lymph nodes, spleen and liver, and a non-inflamed spleen was observed in immunized animals 9 months after the challenge infection. CONCLUSIONS: Our results demonstrate that an ID vaccination using LdCen-/-parasites in combination with sand fly Salivary Protein LJM19 has the capability to confer long lasting protection against visceral leishmaniasis that is comparable to intravenous or intracardial immunization.
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a sand fly Salivary Protein vaccine shows efficacy against vector transmitted cutaneous leishmaniasis in nonhuman primates
Science Translational Medicine, 2015Co-Authors: Fabiano Oliveira, Clarissa Teixeira, Maha Abdeladhim, Edgar D Rowton, Hamide Aslan, Regis Gomes, Philip Castrovinci, Patricia H AlvarengaAbstract:Currently, there are no commercially available human vaccines against leishmaniasis. In rodents, cellular immunity to Salivary Proteins of sand fly vectors is associated to protection against leishmaniasis, making them worthy targets for further exploration as vaccines. We demonstrate that nonhuman primates (NHP) exposed to Phlebotomus duboscqi uninfected sand fly bites or immunized with Salivary Protein PdSP15 are protected against cutaneous leishmaniasis initiated by infected bites. Uninfected sand fly-exposed and 7 of 10 PdSP15-immunized rhesus macaques displayed a significant reduction in disease and parasite burden compared to controls. Protection correlated to the early appearance of Leishmania-specific CD4(+)IFN-I³(+) lymphocytes, suggesting that immunity to saliva or PdSP15 augments the host immune response to the parasites while maintaining minimal pathology. Notably, the 30% unprotected PdSP15-immunized NHP developed neither immunity to PdSP15 nor an accelerated Leishmania-specific immunity. Sera and peripheral blood mononuclear cells from individuals naturally exposed to P. duboscqi bites recognized PdSP15, demonstrating its immunogenicity in humans. PdSP15 sequence and structure show no homology to mammalian Proteins, further demonstrating its potential as a component of a vaccine for human leishmaniasis.
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a listeria monocytogenes based vaccine that secretes sand fly Salivary Protein ljm11 confers long term protection against vector transmitted leishmania major
Infection and Immunity, 2014Co-Authors: Delbert Abi S Abdallah, Jesus G Valenzuela, Claudio Meneses, Fabiano Oliveira, Shaden Kamhawi, Alan Pavinski Bitar, Justin J Park, Susana Mendez, Helene MarquisAbstract:Cutaneous leishmaniasis is a sand fly-transmitted disease characterized by skin ulcers that carry significant scarring and social stigmatization. Over the past years, there has been cumulative evidence that immunity to specific sand fly Salivary Proteins confers a significant level of protection against leishmaniasis. In this study, we used an attenuated strain of Listeria monocytogenes as a vaccine expression system for LJM11, a sand fly Salivary Protein identified as a good vaccine candidate. We observed that mice were best protected against an intradermal needle challenge with Leishmania major and sand fly saliva when vaccinated intravenously. However, this protection was short-lived. Importantly, groups of vaccinated mice were protected long term when challenged with infected sand flies. Protection correlated with smaller lesion size, fewer scars, and better parasite control between 2 and 6 weeks postchallenge compared to the control group of mice vaccinated with the parent L. monocytogenes strain not expressing LJM11. Moreover, protection correlated with high numbers of CD4(+), gamma interferon-positive (IFN-γ(+)), tumor necrosis factor alpha-positive/negative (TNF-α(+/-)), interleukin-10-negative (IL-10(-)) cells and low numbers of CD4(+) IFN-γ(+/-) TNF-α(-) IL-10(+) T cells at 2 weeks postchallenge. Overall, our data indicate that delivery of LJM11 by Listeria is a promising vaccination strategy against cutaneous leishmaniasis inducing long-term protection against ulcer formation following a natural challenge with infected sand flies.
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functional transcriptomics of wild caught lutzomyia intermedia Salivary glands identification of a protective Salivary Protein against leishmania braziliensis infection
PLOS Neglected Tropical Diseases, 2013Co-Authors: Tatiana R De Moura, Claudia Brodskyn, Fabiano Oliveira, Jose Carlos Miranda, Manoel Barralnetto, Marcia W Carneiro, Jorge Clarencio, Aldina BarralAbstract:Background: Leishmania parasites are transmitted in the presence of sand fly saliva. Together with the parasite, the sand fly injects Salivary components that change the environment at the feeding site. Mice immunized with Phlebotomus papatasi Salivary gland (SG) homogenate are protected against Leishmania major infection, while immunity to Lutzomyia intermedia SG homogenate exacerbated experimental Leishmania braziliensis infection. In humans, antibodies to Lu. intermedia saliva are associated with risk of acquiring L. braziliensis infection. Despite these important findings, there is no information regarding the repertoire of Lu. intermedia Salivary Proteins. Methods and Findings: A cDNA library from the Salivary Glands (SGs) of wild-caught Lu. intermedia was constructed, sequenced, and complemented by a proteomic approach based on 1D SDS PAGE and mass/mass spectrometry to validate the transcripts present in this cDNA library. We identified the most abundant transcripts and Proteins reported in other sand fly species as well as novel Proteins such as neurotoxin-like Proteins, peptides with ML domain, and three small peptides found so far only in this sand fly species. DNA plasmids coding for ten selected transcripts were constructed and used to immunize BALB/c mice to study their immunogenicity. Plasmid Linb-11—coding for a 4.5-kDa Protein—induced a cellular immune response and conferred protection against L. braziliensis infection. This protection correlated with a decreased parasite load and an increased frequency of IFN-c-producing cells. Conclusions: We identified the most abundant and novel Proteins present in the SGs of Lu. intermedia, a vector of cutaneous leishmaniasis in the Americas. We also show for the first time that immunity to a single Salivary Protein from Lu. intermedia can protect against cutaneous leishmaniasis caused by L. braziliensis.
Clarissa Teixeira - One of the best experts on this subject based on the ideXlab platform.
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immunization with ljm11 Salivary Protein protects against infection with leishmania braziliensis in the presence of lutzomyia longipalpis saliva
Acta Tropica, 2018Co-Authors: Jurema Cunha, Melissa Abbehusen, Martha Suarez, Clarissa Teixeira, Claudia Brodskyn, Jesus G ValenzuelaAbstract:Abstract Leishmania is transmitted in the presence of sand fly saliva. Protective immunity generated by saliva has encouraged identification of a vector Salivary-based vaccine. Previous studies have shown that immunization with LJM11, a Salivary Protein from Lutzomyia longipalpis, is able to induce a Th1 immune response and protect mice against bites of Leishmania major -infected Lutzomyia longipalpis . Here, we further investigate if immunization with LJM11 recombinant Protein is able to confer cross-protection against infection with Leishmania braziliensis associated with Salivary gland sonicate (SGS) from Lutzomyia intermedia or Lu. longipalpis . Mice immunized with LJM11 Protein exhibited an increased production of anti-LJM11 IgG, IgG1 and IgG2a and a DTH response characterized by an inflammatory infiltrate with the presence of CD4 + IFN-γ + T cells. LJM11-immunized mice were intradermally infected in the ear with L. braziliensis in the presence of Lu. longipalpis or Lu. intermedia SGS. A significant reduction of parasite numbers in the ear and lymph node in the group challenged with L. braziliensis plus Lu. longipalpis SGS was observed, but not when the challenge was performed with L. braziliensis plus Lu. intermedia SGS. A higher specific production of IFN-γ and absence of IL-10 by lymph node cells were only observed in LJM11 immunized mice after infection. After two weeks, a similar frequency of CD4 + IFN-γ + T cells was detected in LJM11 and BSA groups challenged with L. braziliensis plus Lu. longipalpis SGS, suggesting that early events possibly triggered by immunization are essential for protection against Leishmania infection. Our findings support the specificity of saliva-mediated immune responses and reinforce the importance of identifying cross-protective Salivary antigens.
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a sand fly Salivary Protein vaccine shows efficacy against vector transmitted cutaneous leishmaniasis in nonhuman primates
Science Translational Medicine, 2015Co-Authors: Fabiano Oliveira, Clarissa Teixeira, Maha Abdeladhim, Edgar D Rowton, Hamide Aslan, Regis Gomes, Philip Castrovinci, Patricia H AlvarengaAbstract:Currently, there are no commercially available human vaccines against leishmaniasis. In rodents, cellular immunity to Salivary Proteins of sand fly vectors is associated to protection against leishmaniasis, making them worthy targets for further exploration as vaccines. We demonstrate that nonhuman primates (NHP) exposed to Phlebotomus duboscqi uninfected sand fly bites or immunized with Salivary Protein PdSP15 are protected against cutaneous leishmaniasis initiated by infected bites. Uninfected sand fly-exposed and 7 of 10 PdSP15-immunized rhesus macaques displayed a significant reduction in disease and parasite burden compared to controls. Protection correlated to the early appearance of Leishmania-specific CD4(+)IFN-I³(+) lymphocytes, suggesting that immunity to saliva or PdSP15 augments the host immune response to the parasites while maintaining minimal pathology. Notably, the 30% unprotected PdSP15-immunized NHP developed neither immunity to PdSP15 nor an accelerated Leishmania-specific immunity. Sera and peripheral blood mononuclear cells from individuals naturally exposed to P. duboscqi bites recognized PdSP15, demonstrating its immunogenicity in humans. PdSP15 sequence and structure show no homology to mammalian Proteins, further demonstrating its potential as a component of a vaccine for human leishmaniasis.
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immunity to a Salivary Protein of a sand fly vector protects against the fatal outcome of visceral leishmaniasis in a hamster model
Proceedings of the National Academy of Sciences of the United States of America, 2008Co-Authors: Clarissa Teixeira, Fabiano Oliveira, Regis Gomes, Maria Jânia Teixeira, Maria Jose Menezes, Claire Silva, Camila I De OliveiraAbstract:Visceral leishmaniasis (VL) is a fatal disease for humans, and no vaccine is currently available. Sand fly Salivary Proteins have been associated with protection against cutaneous leishmaniasis. To test whether vector Salivary Proteins can protect against VL, a hamster model was developed involving intradermal inoculation in the ears of 100,000 Leishmania infantum chagasi parasites together with Lutzomyia longipalpis saliva to mimic natural transmission by sand flies. Hamsters developed classical signs of VL rapidly, culminating in a fatal outcome 5–6 months postinfection. Saliva had no effect on the course of infection in this model. Immunization with 16 DNA plasmids coding for Salivary Proteins of Lu. longipalpis resulted in the identification of LJM19, a novel 11-kDa Protein, that protected hamsters against the fatal outcome of VL. LJM19-immunized hamsters maintained a low parasite load that correlated with an overall high IFN-γ/TGF-β ratio and inducible NOS expression in the spleen and liver up to 5 months postinfection. Importantly, a delayed-type hypersensitivity response with high expression of IFN-γ was also noted in the skin of LJM19-immunized hamsters 48 h after exposure to uninfected sand fly bites. Induction of IFN-γ at the site of bite could partly explain the protection observed in the viscera of LJM19-immunized hamsters through direct parasite killing and/or priming of anti-Leishmania immunity. We have shown that immunity to a defined Salivary Protein (LJM19) confers powerful protection against the fatal outcome of a parasitic disease, which reinforces the concept of using components of arthropod saliva in vaccine strategies against vector-borne diseases.
Rob C Schuurink - One of the best experts on this subject based on the ideXlab platform.
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the Salivary Protein repertoire of the polyphagous spider mite tetranychus urticae a quest for effectors
Molecular & Cellular Proteomics, 2016Co-Authors: Wim Jonckheere, Wannes Dermauw, Vladimir Zhurov, Nicky Wybouw, Jan Van Den Bulcke, Carlos A Villarroel, Robert Greenhalgh, Mike Grbic, Rob C SchuurinkAbstract:The two-spotted spider mite Tetranychus urticae is an extremely polyphagous crop pest. Alongside an unparalleled detoxification potential for plant secondary metabolites, it has recently been shown that spider mites can attenuate or even suppress plant defenses. Salivary constituents, notably effectors, have been proposed to play an important role in manipulating plant defenses and might determine the outcome of plant-mite interactions. Here, the proteomic composition of saliva from T. urticae lines adapted to various host plants—bean, maize, soy, and tomato—was analyzed using a custom-developed feeding assay coupled with nano-LC tandem mass spectrometry. About 90 putative T. urticae Salivary Proteins were identified. Many are of unknown function, and in numerous cases belonging to multimembered gene families. RNAseq expression analysis revealed that many genes coding for these Salivary Proteins were highly expressed in the proterosoma, the mite body region that includes the Salivary glands. A subset of genes encoding putative Salivary Proteins was selected for whole-mount in situ hybridization, and were found to be expressed in the anterior and dorsal podocephalic glands. Strikingly, host plant dependent expression was evident for putative Salivary Proteins, and was further studied in detail by micro-array based genome-wide expression profiling. This meta-analysis revealed for the first time the Salivary Protein repertoire of a phytophagous chelicerate. The availability of this Salivary proteome will assist in unraveling the molecular interface between phytophagous mites and their host plants, and may ultimately facilitate the development of mite-resistant crops. Furthermore, the technique used in this study is a time- and resource-efficient method to examine the Salivary Protein composition of other small arthropods for which saliva or Salivary glands cannot be isolated easily.
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The Salivary Protein Repertoire of the Polyphagous Spider Mite Tetranychus urticae: A Quest for Effectors *
Molecular & cellular proteomics : MCP, 2016Co-Authors: Wim Jonckheere, Wannes Dermauw, Vladimir Zhurov, Nicky Wybouw, Jan Van Den Bulcke, Carlos A Villarroel, Robert Greenhalgh, Rob C Schuurink, Mike Grbić, Luc TirryAbstract:The two-spotted spider mite Tetranychus urticae is an extremely polyphagous crop pest. Alongside an unparalleled detoxification potential for plant secondary metabolites, it has recently been shown that spider mites can attenuate or even suppress plant defenses. Salivary constituents, notably effectors, have been proposed to play an important role in manipulating plant defenses and might determine the outcome of plant-mite interactions. Here, the proteomic composition of saliva from T. urticae lines adapted to various host plants—bean, maize, soy, and tomato—was analyzed using a custom-developed feeding assay coupled with nano-LC tandem mass spectrometry. About 90 putative T. urticae Salivary Proteins were identified. Many are of unknown function, and in numerous cases belonging to multimembered gene families. RNAseq expression analysis revealed that many genes coding for these Salivary Proteins were highly expressed in the proterosoma, the mite body region that includes the Salivary glands. A subset of genes encoding putative Salivary Proteins was selected for whole-mount in situ hybridization, and were found to be expressed in the anterior and dorsal podocephalic glands. Strikingly, host plant dependent expression was evident for putative Salivary Proteins, and was further studied in detail by micro-array based genome-wide expression profiling. This meta-analysis revealed for the first time the Salivary Protein repertoire of a phytophagous chelicerate. The availability of this Salivary proteome will assist in unraveling the molecular interface between phytophagous mites and their host plants, and may ultimately facilitate the development of mite-resistant crops. Furthermore, the technique used in this study is a time- and resource-efficient method to examine the Salivary Protein composition of other small arthropods for which saliva or Salivary glands cannot be isolated easily.
Jesus G Valenzuela - One of the best experts on this subject based on the ideXlab platform.
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comparative evolution of sand fly Salivary Protein families and implications for biomarkers of vector exposure and Salivary vaccine candidates
Frontiers in Cellular and Infection Microbiology, 2018Co-Authors: Iliano V Coutinhoabreu, Jesus G ValenzuelaAbstract:Sand fly Salivary Proteins that produce a specific antibody response in humans and animal reservoirs have been shown to be promising biomarkers of sand fly exposure. Furthermore, immunity to sand fly Salivary Proteins were shown to protect rodents and non-human primates against Leishmania infection. We are missing critical information regarding the divergence amongst sand fly Salivary Proteins from different sand fly vectors, a knowledge that will support the search of broad or specific Salivary biomarkers of vector exposure and those for vaccines components against leishmaniasis. Here, we compare the molecular evolution of the Salivary Protein families in New World and Old World sand flies from 14 different sand fly vectors. We found that the Protein families unique to OW sand flies are more conserved than those unique to NW sand flies regarding both sequence polymorphisms and copy number variation. In addition, the Protein families unique to OW sand flies do not display as many conserved cysteine residues as the one unique to the NW group (28.5% in OW vs. 62.5% in NW). Moreover, the expression of specific Protein families is restricted to the Salivary glands of unique sand fly taxon. For instance, the ParSP15 family is unique to the Larroussius subgenus whereas phospholipase A2 is only expressed in member of Larroussius and Adlerius subgenera. The SP2.5-like family is only expressed in members of the Phlebotomus and Paraphlebotomus subgenera. The sequences shared between OW and NW sand flies have diverged at similar rates (38.7 and 45.3% amino acid divergence, respectively), yet differences in gene copy number were evident across Protein families and sand fly species. Overall, this comparative analysis sheds light on the different modes of sand fly Salivary Protein family divergence. Also, it informs which Protein families are unique and conserved within taxon for the choice of taxon-specific biomarkers of vector exposure, as well as those families more conserved across taxa to be used as pan-specific vaccines for leishmaniasis.
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immunization with ljm11 Salivary Protein protects against infection with leishmania braziliensis in the presence of lutzomyia longipalpis saliva
Acta Tropica, 2018Co-Authors: Jurema Cunha, Melissa Abbehusen, Martha Suarez, Clarissa Teixeira, Claudia Brodskyn, Jesus G ValenzuelaAbstract:Abstract Leishmania is transmitted in the presence of sand fly saliva. Protective immunity generated by saliva has encouraged identification of a vector Salivary-based vaccine. Previous studies have shown that immunization with LJM11, a Salivary Protein from Lutzomyia longipalpis, is able to induce a Th1 immune response and protect mice against bites of Leishmania major -infected Lutzomyia longipalpis . Here, we further investigate if immunization with LJM11 recombinant Protein is able to confer cross-protection against infection with Leishmania braziliensis associated with Salivary gland sonicate (SGS) from Lutzomyia intermedia or Lu. longipalpis . Mice immunized with LJM11 Protein exhibited an increased production of anti-LJM11 IgG, IgG1 and IgG2a and a DTH response characterized by an inflammatory infiltrate with the presence of CD4 + IFN-γ + T cells. LJM11-immunized mice were intradermally infected in the ear with L. braziliensis in the presence of Lu. longipalpis or Lu. intermedia SGS. A significant reduction of parasite numbers in the ear and lymph node in the group challenged with L. braziliensis plus Lu. longipalpis SGS was observed, but not when the challenge was performed with L. braziliensis plus Lu. intermedia SGS. A higher specific production of IFN-γ and absence of IL-10 by lymph node cells were only observed in LJM11 immunized mice after infection. After two weeks, a similar frequency of CD4 + IFN-γ + T cells was detected in LJM11 and BSA groups challenged with L. braziliensis plus Lu. longipalpis SGS, suggesting that early events possibly triggered by immunization are essential for protection against Leishmania infection. Our findings support the specificity of saliva-mediated immune responses and reinforce the importance of identifying cross-protective Salivary antigens.
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intradermal immunization of leishmania donovani centrin knock out parasites in combination with Salivary Protein ljm19 from sand fly vector induces a durable protective immune response in hamsters
PLOS Neglected Tropical Diseases, 2016Co-Authors: Jesus G Valenzuela, Jacqueline Araujo Fiuza, Dwann Davenport, Maha Abdeladhim, Claudio Meneses, Fabiano Oliveira, Shaden Kamhawi, Sreenivas Gannavaram, Hira L NakhasiAbstract:BACKGROUND: Visceral leishmaniasis (VL) is a neglected tropical disease and is fatal if untreated. There is no vaccine available against leishmaniasis. The majority of patients with cutaneous leishmaniasis (CL) or VL develop a long-term protective immunity after cure from infection, which indicates that development of an effective vaccine against leishmaniasis is possible. Such protection may also be achieved by immunization with live attenuated parasites that do not cause disease. We have previously reported a protective response in mice, hamsters and dogs with Leishmania donovani centrin gene knock-out parasites (LdCen-/-), a live attenuated parasite with a cell division specific centrin1 gene deletion. In this study we have explored the effects of Salivary Protein LJM19 as an adjuvant and intradermal (ID) route of immunization on the efficacy of LdCen-/- parasites as a vaccine against virulent L. donovani. METHODOLOGY/PRINCIPAL FINDINGS: To explore the potential of a combination of LdCen-/- parasites and Salivary Protein LJM19 as vaccine antigens, LdCen-/- ID immunization followed by ID challenge with virulent L. donovani were performed in hamsters in a 9-month follow up study. We determined parasite burden (serial dilution), antibody production (ELISA) and cytokine expression (qPCR) in these animals. Compared to controls, animals immunized with LdCen-/- + LJM19 induced a strong antibody response, a reduction in spleen and liver parasite burden and a higher expression of pro-inflammatory cytokines after immunization and one month post-challenge. Additionally, a low parasite load in lymph nodes, spleen and liver, and a non-inflamed spleen was observed in immunized animals 9 months after the challenge infection. CONCLUSIONS: Our results demonstrate that an ID vaccination using LdCen-/-parasites in combination with sand fly Salivary Protein LJM19 has the capability to confer long lasting protection against visceral leishmaniasis that is comparable to intravenous or intracardial immunization.
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a listeria monocytogenes based vaccine that secretes sand fly Salivary Protein ljm11 confers long term protection against vector transmitted leishmania major
Infection and Immunity, 2014Co-Authors: Delbert Abi S Abdallah, Jesus G Valenzuela, Claudio Meneses, Fabiano Oliveira, Shaden Kamhawi, Alan Pavinski Bitar, Justin J Park, Susana Mendez, Helene MarquisAbstract:Cutaneous leishmaniasis is a sand fly-transmitted disease characterized by skin ulcers that carry significant scarring and social stigmatization. Over the past years, there has been cumulative evidence that immunity to specific sand fly Salivary Proteins confers a significant level of protection against leishmaniasis. In this study, we used an attenuated strain of Listeria monocytogenes as a vaccine expression system for LJM11, a sand fly Salivary Protein identified as a good vaccine candidate. We observed that mice were best protected against an intradermal needle challenge with Leishmania major and sand fly saliva when vaccinated intravenously. However, this protection was short-lived. Importantly, groups of vaccinated mice were protected long term when challenged with infected sand flies. Protection correlated with smaller lesion size, fewer scars, and better parasite control between 2 and 6 weeks postchallenge compared to the control group of mice vaccinated with the parent L. monocytogenes strain not expressing LJM11. Moreover, protection correlated with high numbers of CD4(+), gamma interferon-positive (IFN-γ(+)), tumor necrosis factor alpha-positive/negative (TNF-α(+/-)), interleukin-10-negative (IL-10(-)) cells and low numbers of CD4(+) IFN-γ(+/-) TNF-α(-) IL-10(+) T cells at 2 weeks postchallenge. Overall, our data indicate that delivery of LJM11 by Listeria is a promising vaccination strategy against cutaneous leishmaniasis inducing long-term protection against ulcer formation following a natural challenge with infected sand flies.
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dna vaccination with kmp11 and lutzomyia longipalpis Salivary Protein protects hamsters against visceral leishmaniasis
Acta Tropica, 2011Co-Authors: Natalia Tavares, Dirceu Costa, Maiana Pitombo, Jose Carlos Miranda, Camila I De Oliveira, Robson A Da Silva, Larissa Barbosa, Kyioshi Fukutani, Jesus G ValenzuelaAbstract:It was recently shown that immunization of hamsters with DNA plasmids coding LJM19, a sand fly Salivary Protein, partially protected against a challenge with Leishmania chagasi, whereas immunization with KMP11 DNA plasmid, a Leishmania antigen, induced protection against L. donovani infection. In the present study, we evaluated the protective effect of immunization with both LJM19 and KMP11 DNA plasmid together. Concerning the protection against an infection by L. chagasi, immunization with DNA plasmids coding LJM19 or KMP11, as well as with both plasmids combined, induced IFN-I³ production in draining lymph nodes at 7, 14 and 21 days post-immunization. Immunized hamsters challenged with L. chagasi plus Salivary Gland Sonicate (SGS) from Lutzomyia longipalpis showed an enhancement of IFN-I³/IL-10 and IFN-I³/TGF-s in draining lymph nodes after 7 and 14 days of infection. Two and five months after challenge, immunized animals showed reduced parasite load in the liver and spleen, as well as increased IFN-I³/IL-10 and IFN-I³/TGF-s ratios in the spleen. Furthermore, immunized animals remained with a normal hematological profile even five months after the challenge, whereas L. chagasi in unimmunized hamsters lead to a significant anemia. The protection observed with LJM19 or KMP11 DNA plasmids used alone was very similar to the protection obtained by the combination of both plasmids
