Biochemical Characterization and Evaluation of a Brugia malayi Small Heat Shock Protein as a Vaccine against Lymphatic Filariasis
Identifieur interne : 004494 ( Main/Exploration ); précédent : 004493; suivant : 004495Biochemical Characterization and Evaluation of a Brugia malayi Small Heat Shock Protein as a Vaccine against Lymphatic Filariasis
Auteurs : Gajalakshmi Dakshinamoorthy [États-Unis] ; Abhilash Kumble Samykutty [États-Unis, Inde] ; Gnanasekar Munirathinam [États-Unis] ; Gangadhar Bhaurao Shinde [Inde] ; Thomas Nutman [États-Unis] ; Maryada Venkatarami Reddy [Inde] ; Ramaswamy Kalyanasundaram [États-Unis]Source :
- PLoS ONE [ 1932-6203 ] ; 2012.
Descripteurs français
- KwdFr :
- Animaux, Anticorps antihelminthe (immunologie), Anticorps antihelminthe (sang), Antigènes d'helminthe (immunologie), Brugia malayi (immunologie), Cytokines (métabolisme), Cytotoxicité à médiation cellulaire dépendante des anticorps, Données de séquences moléculaires, Filariose lymphatique (), Filariose lymphatique (immunologie), Fragments peptidiques (immunologie), Humains, Immunoglobuline G (immunologie), Interleukine-10 (immunologie), Interleukine-10 (métabolisme), Mastocytes (cytologie), Mastocytes (métabolisme), Mâle, Petites protéines du choc thermique (génétique), Petites protéines du choc thermique (immunologie), Petites protéines du choc thermique (métabolisme), Prolifération cellulaire, Protéines recombinantes (génétique), Protéines recombinantes (immunologie), Rate (cytologie), Rate (immunologie), Rate (métabolisme), Récepteurs à l'interleukine-10 (immunologie), Récepteurs à l'interleukine-10 (métabolisme), Souris, Souris de lignée BALB C, Séquence d'acides aminés, Vaccination, Vaccins à ADN (usage thérapeutique).
- MESH :
- cytologie : Mastocytes, Rate.
- génétique : Petites protéines du choc thermique, Protéines recombinantes.
- immunologie : Anticorps antihelminthe, Antigènes d'helminthe, Brugia malayi, Filariose lymphatique, Fragments peptidiques, Immunoglobuline G, Interleukine-10, Petites protéines du choc thermique, Protéines recombinantes, Rate, Récepteurs à l'interleukine-10.
- métabolisme : Cytokines, Interleukine-10, Mastocytes, Petites protéines du choc thermique, Rate, Récepteurs à l'interleukine-10.
- sang : Anticorps antihelminthe.
- usage thérapeutique : Vaccins à ADN.
- Animaux, Cytotoxicité à médiation cellulaire dépendante des anticorps, Données de séquences moléculaires, Filariose lymphatique, Humains, Mâle, Prolifération cellulaire, Souris, Souris de lignée BALB C, Séquence d'acides aminés, Vaccination.
English descriptors
- KwdEn :
- Amino Acid Sequence, Animals, Antibodies, Helminth (blood), Antibodies, Helminth (immunology), Antibody-Dependent Cell Cytotoxicity, Antigens, Helminth (immunology), Brugia malayi (immunology), Cell Proliferation, Cytokines (metabolism), Elephantiasis, Filarial (immunology), Elephantiasis, Filarial (prevention & control), Heat-Shock Proteins, Small (genetics), Heat-Shock Proteins, Small (immunology), Heat-Shock Proteins, Small (metabolism), Humans, Immunoglobulin G (immunology), Interleukin-10 (immunology), Interleukin-10 (metabolism), Male, Mast Cells (cytology), Mast Cells (metabolism), Mice, Mice, Inbred BALB C, Molecular Sequence Data, Peptide Fragments (immunology), Receptors, Interleukin-10 (immunology), Receptors, Interleukin-10 (metabolism), Recombinant Proteins (genetics), Recombinant Proteins (immunology), Spleen (cytology), Spleen (immunology), Spleen (metabolism), Vaccination, Vaccines, DNA (therapeutic use).
- MESH :
- chemical , blood : Antibodies, Helminth.
- chemical , genetics : Heat-Shock Proteins, Small, Recombinant Proteins.
- chemical , immunology : Antibodies, Helminth, Antigens, Helminth, Heat-Shock Proteins, Small, Immunoglobulin G, Interleukin-10, Peptide Fragments, Receptors, Interleukin-10, Recombinant Proteins.
- cytology : Mast Cells, Spleen.
- immunology : Brugia malayi, Elephantiasis, Filarial, Spleen.
- chemical , metabolism : Cytokines, Heat-Shock Proteins, Small, Interleukin-10, Mast Cells, Receptors, Interleukin-10, Spleen.
- prevention & control : Elephantiasis, Filarial.
- chemical , therapeutic use : Vaccines, DNA.
- Amino Acid Sequence, Animals, Antibody-Dependent Cell Cytotoxicity, Cell Proliferation, Humans, Male, Mice, Mice, Inbred BALB C, Molecular Sequence Data, Vaccination.
Abstract
Filarial nematodes enjoy one of the longest life spans of any human pathogen due to effective immune evasion strategies developed by the parasite. Among the various immune evasion strategies exhibited by the parasite, Interleukin 10 (IL-10) productions and IL-10 mediated immune suppression has significant negative impact on the host immune system. Recently, we identified a small heat shock protein expressed by
Url:
DOI: 10.1371/journal.pone.0034077
PubMed: 22496777
PubMed Central: 3320633
Affiliations:
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Le document en format XML
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Heat Shock Protein as a Vaccine against Lymphatic Filariasis</title><author><name sortKey="Dakshinamoorthy, Gajalakshmi" sort="Dakshinamoorthy, Gajalakshmi" uniqKey="Dakshinamoorthy G" first="Gajalakshmi" last="Dakshinamoorthy">Gajalakshmi Dakshinamoorthy</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Department of Biomedical Sciences, University of Illinois College of Medicine at Rockford, Rockford, Illinois, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biomedical Sciences, University of Illinois College of Medicine at Rockford, Rockford, Illinois</wicri:regionArea><placeName><region type="state">Illinois</region></placeName></affiliation></author><author><name sortKey="Samykutty, Abhilash Kumble" sort="Samykutty, Abhilash Kumble" uniqKey="Samykutty A" first="Abhilash Kumble" last="Samykutty">Abhilash Kumble Samykutty</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Department 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Munirathinam</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Department of Biomedical Sciences, University of Illinois College of Medicine at Rockford, Rockford, Illinois, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biomedical Sciences, University of Illinois College of Medicine at Rockford, Rockford, Illinois</wicri:regionArea><placeName><region type="state">Illinois</region></placeName></affiliation></author><author><name sortKey="Shinde, Gangadhar Bhaurao" sort="Shinde, Gangadhar Bhaurao" uniqKey="Shinde G" first="Gangadhar Bhaurao" last="Shinde">Gangadhar Bhaurao Shinde</name><affiliation wicri:level="1"><nlm:aff id="aff3"><addr-line>Department of Biochemistry, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur, Maharashtra, India</addr-line></nlm:aff><country xml:lang="fr">Inde</country><wicri:regionArea>Department of Biochemistry, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur, Maharashtra</wicri:regionArea><wicri:noRegion>Maharashtra</wicri:noRegion></affiliation></author><author><name sortKey="Nutman, Thomas" sort="Nutman, Thomas" uniqKey="Nutman T" first="Thomas" last="Nutman">Thomas Nutman</name><affiliation wicri:level="2"><nlm:aff id="aff4"><addr-line>Helminth Immunology Section, National Institutes of Health, Bethesda, Maryland, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Helminth Immunology Section, National Institutes of Health, Bethesda, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Reddy, Maryada Venkatarami" sort="Reddy, Maryada Venkatarami" uniqKey="Reddy M" first="Maryada Venkatarami" last="Reddy">Maryada Venkatarami Reddy</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Department of Biochemistry, Mahatma Gandhi Institute of Medical Sciences, Sevagram, Maharashtra, India</addr-line></nlm:aff><country xml:lang="fr">Inde</country><wicri:regionArea>Department of Biochemistry, Mahatma Gandhi Institute of Medical Sciences, Sevagram, Maharashtra</wicri:regionArea><wicri:noRegion>Maharashtra</wicri:noRegion></affiliation></author><author><name sortKey="Kalyanasundaram, Ramaswamy" sort="Kalyanasundaram, Ramaswamy" uniqKey="Kalyanasundaram R" first="Ramaswamy" last="Kalyanasundaram">Ramaswamy Kalyanasundaram</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Department of Biomedical Sciences, University of Illinois College of Medicine at Rockford, Rockford, Illinois, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biomedical Sciences, University of Illinois College of Medicine at Rockford, Rockford, Illinois</wicri:regionArea><placeName><region type="state">Illinois</region></placeName></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Sequence</term><term>Animals</term><term>Antibodies, Helminth (blood)</term><term>Antibodies, Helminth (immunology)</term><term>Antibody-Dependent Cell Cytotoxicity</term><term>Antigens, Helminth (immunology)</term><term>Brugia malayi (immunology)</term><term>Cell Proliferation</term><term>Cytokines (metabolism)</term><term>Elephantiasis, Filarial (immunology)</term><term>Elephantiasis, Filarial (prevention & control)</term><term>Heat-Shock Proteins, Small (genetics)</term><term>Heat-Shock Proteins, Small (immunology)</term><term>Heat-Shock Proteins, Small (metabolism)</term><term>Humans</term><term>Immunoglobulin G (immunology)</term><term>Interleukin-10 (immunology)</term><term>Interleukin-10 (metabolism)</term><term>Male</term><term>Mast Cells (cytology)</term><term>Mast Cells (metabolism)</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Molecular Sequence Data</term><term>Peptide Fragments (immunology)</term><term>Receptors, Interleukin-10 (immunology)</term><term>Receptors, Interleukin-10 (metabolism)</term><term>Recombinant Proteins (genetics)</term><term>Recombinant Proteins (immunology)</term><term>Spleen (cytology)</term><term>Spleen (immunology)</term><term>Spleen (metabolism)</term><term>Vaccination</term><term>Vaccines, DNA (therapeutic use)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Anticorps antihelminthe (immunologie)</term><term>Anticorps antihelminthe (sang)</term><term>Antigènes d'helminthe (immunologie)</term><term>Brugia malayi (immunologie)</term><term>Cytokines (métabolisme)</term><term>Cytotoxicité à médiation cellulaire dépendante des anticorps</term><term>Données de séquences moléculaires</term><term>Filariose lymphatique ()</term><term>Filariose lymphatique (immunologie)</term><term>Fragments peptidiques (immunologie)</term><term>Humains</term><term>Immunoglobuline G (immunologie)</term><term>Interleukine-10 (immunologie)</term><term>Interleukine-10 (métabolisme)</term><term>Mastocytes (cytologie)</term><term>Mastocytes (métabolisme)</term><term>Mâle</term><term>Petites protéines du choc thermique (génétique)</term><term>Petites protéines du choc thermique (immunologie)</term><term>Petites protéines du choc thermique (métabolisme)</term><term>Prolifération cellulaire</term><term>Protéines recombinantes (génétique)</term><term>Protéines recombinantes (immunologie)</term><term>Rate (cytologie)</term><term>Rate (immunologie)</term><term>Rate (métabolisme)</term><term>Récepteurs à l'interleukine-10 (immunologie)</term><term>Récepteurs à l'interleukine-10 (métabolisme)</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Séquence d'acides aminés</term><term>Vaccination</term><term>Vaccins à ADN (usage thérapeutique)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>Antibodies, Helminth</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Heat-Shock Proteins, Small</term><term>Recombinant Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Antibodies, Helminth</term><term>Antigens, Helminth</term><term>Heat-Shock Proteins, Small</term><term>Immunoglobulin G</term><term>Interleukin-10</term><term>Peptide Fragments</term><term>Receptors, Interleukin-10</term><term>Recombinant Proteins</term></keywords><keywords scheme="MESH" qualifier="cytologie" xml:lang="fr"><term>Mastocytes</term><term>Rate</term></keywords><keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>Mast Cells</term><term>Spleen</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Petites protéines du choc thermique</term><term>Protéines recombinantes</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Anticorps antihelminthe</term><term>Antigènes d'helminthe</term><term>Brugia malayi</term><term>Filariose lymphatique</term><term>Fragments peptidiques</term><term>Immunoglobuline G</term><term>Interleukine-10</term><term>Petites protéines du choc thermique</term><term>Protéines recombinantes</term><term>Rate</term><term>Récepteurs à l'interleukine-10</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Brugia malayi</term><term>Elephantiasis, Filarial</term><term>Spleen</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Cytokines</term><term>Heat-Shock Proteins, Small</term><term>Interleukin-10</term><term>Mast Cells</term><term>Receptors, Interleukin-10</term><term>Spleen</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Cytokines</term><term>Interleukine-10</term><term>Mastocytes</term><term>Petites protéines du choc thermique</term><term>Rate</term><term>Récepteurs à l'interleukine-10</term></keywords><keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>Elephantiasis, Filarial</term></keywords><keywords scheme="MESH" qualifier="sang" xml:lang="fr"><term>Anticorps antihelminthe</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Vaccines, DNA</term></keywords><keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Vaccins à ADN</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Amino Acid Sequence</term><term>Animals</term><term>Antibody-Dependent Cell Cytotoxicity</term><term>Cell Proliferation</term><term>Humans</term><term>Male</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Molecular Sequence Data</term><term>Vaccination</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cytotoxicité à médiation cellulaire dépendante des anticorps</term><term>Données de séquences moléculaires</term><term>Filariose lymphatique</term><term>Humains</term><term>Mâle</term><term>Prolifération cellulaire</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Séquence d'acides aminés</term><term>Vaccination</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Filarial nematodes enjoy one of the longest life spans of any human pathogen due to effective immune evasion strategies developed by the parasite. Among the various immune evasion strategies exhibited by the parasite, Interleukin 10 (IL-10) productions and IL-10 mediated immune suppression has significant negative impact on the host immune system. Recently, we identified a small heat shock protein expressed by <italic>Brugia malayi</italic> (BmHsp12.6) that can bind to soluble human IL-10 receptor alpha (IL-10R) and activate IL-10 mediated effects in cell lines. In this study we show that the IL-10R binding region of BmHsp12.6 is localized to its N-terminal region. This region has significant sequence similarity to the receptor binding region of human IL-10. <italic>In vitro</italic> studies confirm that the N-terminal region of BmHsp12.6 (N-BmHsp12.6) has IL-10 like activity and the region containing the alpha crystalline domain and C-terminus of BmHsp12.6 (BmHsp12.6αc) has no IL-10 like activity. However, BmHsp12.6αc contains B cell, T cell and CTL epitopes. Members of the sHSP families are excellent vaccine candidates. Evaluation of sera samples from putatively immune endemic normal (EN) subjects showed IgG1 and IgG3 antibodies against BmHsp12.6αc and these antibodies were involved in the ADCC mediated protection. Subsequent vaccination trials with BmHsp12.6αc in a mouse model using a heterologous prime boost approach showed that 83% protection can be achieved against <italic>B. malayi</italic> L3 challenge. <xref ref-type="sec" rid="s3">Results</xref> presented in this study thus show that the N-BmHsp12.6 subunit of BmHsp12.6 has immunoregulatory function, whereas, the BmHsp12.6αc subunit of BmHsp12.6 has significant vaccine potential.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Michael, E" uniqKey="Michael E">E Michael</name></author><author><name sortKey="Bundy, Da" uniqKey="Bundy D">DA Bundy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hotez, Pj" uniqKey="Hotez P">PJ Hotez</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gregory, Wf" uniqKey="Gregory W">WF Gregory</name></author><author><name sortKey="Atmadja, Ak" uniqKey="Atmadja A">AK 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uniqKey="Hewinson R">RG Hewinson</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Inde</li><li>États-Unis</li></country><region><li>Illinois</li><li>Maryland</li></region></list><tree><country name="États-Unis"><region name="Illinois"><name sortKey="Dakshinamoorthy, Gajalakshmi" sort="Dakshinamoorthy, Gajalakshmi" uniqKey="Dakshinamoorthy G" first="Gajalakshmi" last="Dakshinamoorthy">Gajalakshmi Dakshinamoorthy</name></region><name sortKey="Kalyanasundaram, Ramaswamy" sort="Kalyanasundaram, Ramaswamy" uniqKey="Kalyanasundaram R" first="Ramaswamy" last="Kalyanasundaram">Ramaswamy Kalyanasundaram</name><name sortKey="Munirathinam, Gnanasekar" sort="Munirathinam, Gnanasekar" uniqKey="Munirathinam G" first="Gnanasekar" last="Munirathinam">Gnanasekar Munirathinam</name><name sortKey="Nutman, Thomas" sort="Nutman, Thomas" uniqKey="Nutman T" first="Thomas" last="Nutman">Thomas Nutman</name><name sortKey="Samykutty, Abhilash Kumble" sort="Samykutty, Abhilash Kumble" uniqKey="Samykutty A" first="Abhilash Kumble" last="Samykutty">Abhilash Kumble Samykutty</name></country><country name="Inde"><noRegion><name sortKey="Samykutty, Abhilash Kumble" sort="Samykutty, Abhilash Kumble" uniqKey="Samykutty A" first="Abhilash Kumble" last="Samykutty">Abhilash Kumble Samykutty</name></noRegion><name sortKey="Reddy, Maryada Venkatarami" sort="Reddy, Maryada Venkatarami" uniqKey="Reddy M" first="Maryada Venkatarami" last="Reddy">Maryada Venkatarami Reddy</name><name sortKey="Shinde, Gangadhar Bhaurao" sort="Shinde, Gangadhar Bhaurao" uniqKey="Shinde G" first="Gangadhar Bhaurao" last="Shinde">Gangadhar Bhaurao Shinde</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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