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Recombinant trehalose-6-phosphate phosphatase of Brugia malayi cross-reacts with human Wuchereria bancrofti immune sera and engenders a robust protective outcome in mice.

Identifieur interne : 003F33 ( Main/Exploration ); précédent : 003F32; suivant : 003F34

Recombinant trehalose-6-phosphate phosphatase of Brugia malayi cross-reacts with human Wuchereria bancrofti immune sera and engenders a robust protective outcome in mice.

Auteurs : Susheela Kushwaha [Inde] ; Prashant Kumar Singh ; Jyoti Gupta ; Vishal Kumar Soni ; Shailja Misra-Bhattacharya

Source :

RBID : pubmed:22981601

Descripteurs français

English descriptors

Abstract

Trehalose-6-phosphate phosphatase of Brugia malayi (Bm-TPP) represents an attractive vaccine candidate because it is present in all the major life stages of parasite, but is absent in mammals. We have previously cloned, purified and biochemically characterized Bm-TPP. In the present study, we investigated the cross-reactivity of recombinant Bm-TPP (r-Bm-TPP) with the sera of human bancroftian patients belonging to different disease categories. In silico study using bioinformatics tool demonstrated that Bm-TPP is highly immunogenic in nature. BALB/c mice administered with r-Bm-TPP alone or in combination with Freund's complete adjuvant (FCA) generated a strong IgG response. Further investigations on the antibody isotypes showed generation of a mixed T helper cell response which was marginally biased towards Th1 phenotype. r-Bm-TPP with or without adjuvant lead to significantly increased accumulation of CD4+ and CD8+ T cells in the spleen of infected mice and increased the activation of peritoneal macrophages. Additionally, r-Bm-TPP enhanced the production of both proinflammatory (IL-2, IFN-γ) and anti-inflammatory (IL-4, IL-10) cytokines and mice immunized with r-Bm-TPP alone or in combination with FCA showed 54.5% and 67% protection respectively against B. malayi infective larvae challenge. Taken together, our findings suggest that Bm-TPP is protective in nature and might be a potential candidate for development of vaccine against lymphatic filarial infections.

DOI: 10.1016/j.micinf.2012.08.006
PubMed: 22981601


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Le document en format XML

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<term>Amino Acid Sequence</term>
<term>Analysis of Variance</term>
<term>Animals</term>
<term>Antibodies, Helminth (blood)</term>
<term>Antibodies, Helminth (immunology)</term>
<term>Antibodies, Helminth (metabolism)</term>
<term>Brugia malayi (enzymology)</term>
<term>Brugia malayi (genetics)</term>
<term>Brugia malayi (immunology)</term>
<term>Cell Proliferation</term>
<term>Computational Biology</term>
<term>Computer Simulation</term>
<term>Cross Reactions</term>
<term>Cytokines (immunology)</term>
<term>Cytokines (metabolism)</term>
<term>Elephantiasis, Filarial (immunology)</term>
<term>Helminth Proteins (immunology)</term>
<term>Helminth Proteins (metabolism)</term>
<term>Immunoglobulin G (blood)</term>
<term>Immunoglobulin G (immunology)</term>
<term>Immunoglobulin G (metabolism)</term>
<term>Macrophages</term>
<term>Male</term>
<term>Mice</term>
<term>Mice, Inbred BALB C</term>
<term>Molecular Sequence Data</term>
<term>Phosphoric Monoester Hydrolases (immunology)</term>
<term>Phosphoric Monoester Hydrolases (metabolism)</term>
<term>Recombinant Proteins (immunology)</term>
<term>Recombinant Proteins (metabolism)</term>
<term>Vaccines, Synthetic (immunology)</term>
<term>Wuchereria bancrofti (genetics)</term>
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<term>Analyse de variance</term>
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<term>Anticorps antihelminthe (métabolisme)</term>
<term>Anticorps antihelminthe (sang)</term>
<term>Biologie informatique</term>
<term>Brugia malayi (enzymologie)</term>
<term>Brugia malayi (génétique)</term>
<term>Brugia malayi (immunologie)</term>
<term>Cytokines (immunologie)</term>
<term>Cytokines (métabolisme)</term>
<term>Données de séquences moléculaires</term>
<term>Filariose lymphatique (immunologie)</term>
<term>Immunoglobuline G (immunologie)</term>
<term>Immunoglobuline G (métabolisme)</term>
<term>Immunoglobuline G (sang)</term>
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<term>Mâle</term>
<term>Phosphoric monoester hydrolases (immunologie)</term>
<term>Phosphoric monoester hydrolases (métabolisme)</term>
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<term>Protéines d'helminthes (immunologie)</term>
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<term>Protéines recombinantes (métabolisme)</term>
<term>Réactions croisées</term>
<term>Simulation numérique</term>
<term>Souris</term>
<term>Souris de lignée BALB C</term>
<term>Séquence d'acides aminés</term>
<term>Vaccins synthétiques (immunologie)</term>
<term>Wuchereria bancrofti (génétique)</term>
<term>Wuchereria bancrofti (immunologie)</term>
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<term>Antibodies, Helminth</term>
<term>Immunoglobulin G</term>
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<term>Antibodies, Helminth</term>
<term>Cytokines</term>
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<term>Immunoglobulin G</term>
<term>Phosphoric Monoester Hydrolases</term>
<term>Recombinant Proteins</term>
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<term>Phosphoric Monoester Hydrolases</term>
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<keywords scheme="MESH" qualifier="enzymology" xml:lang="en">
<term>Brugia malayi</term>
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<keywords scheme="MESH" qualifier="genetics" xml:lang="en">
<term>Brugia malayi</term>
<term>Wuchereria bancrofti</term>
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<term>Brugia malayi</term>
<term>Wuchereria bancrofti</term>
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<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr">
<term>Anticorps antihelminthe</term>
<term>Brugia malayi</term>
<term>Cytokines</term>
<term>Filariose lymphatique</term>
<term>Immunoglobuline G</term>
<term>Phosphoric monoester hydrolases</term>
<term>Protéines d'helminthes</term>
<term>Protéines recombinantes</term>
<term>Vaccins synthétiques</term>
<term>Wuchereria bancrofti</term>
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<term>Anticorps antihelminthe</term>
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<term>Phosphoric monoester hydrolases</term>
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<term>Macrophages</term>
<term>Mâle</term>
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<term>Réactions croisées</term>
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<div type="abstract" xml:lang="en">Trehalose-6-phosphate phosphatase of Brugia malayi (Bm-TPP) represents an attractive vaccine candidate because it is present in all the major life stages of parasite, but is absent in mammals. We have previously cloned, purified and biochemically characterized Bm-TPP. In the present study, we investigated the cross-reactivity of recombinant Bm-TPP (r-Bm-TPP) with the sera of human bancroftian patients belonging to different disease categories. In silico study using bioinformatics tool demonstrated that Bm-TPP is highly immunogenic in nature. BALB/c mice administered with r-Bm-TPP alone or in combination with Freund's complete adjuvant (FCA) generated a strong IgG response. Further investigations on the antibody isotypes showed generation of a mixed T helper cell response which was marginally biased towards Th1 phenotype. r-Bm-TPP with or without adjuvant lead to significantly increased accumulation of CD4+ and CD8+ T cells in the spleen of infected mice and increased the activation of peritoneal macrophages. Additionally, r-Bm-TPP enhanced the production of both proinflammatory (IL-2, IFN-γ) and anti-inflammatory (IL-4, IL-10) cytokines and mice immunized with r-Bm-TPP alone or in combination with FCA showed 54.5% and 67% protection respectively against B. malayi infective larvae challenge. Taken together, our findings suggest that Bm-TPP is protective in nature and might be a potential candidate for development of vaccine against lymphatic filarial infections.</div>
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