High-through identification of T cell-specific phage-exposed mimotopes using PBMCs from tegumentary leishmaniasis patients and their use as vaccine candidates against Leishmania amazonensis infection
In the current study, phage-exposed mimotopes as targets against tegumentary leishmaniasis (TL) were selected by means of bio-panning cycles employing sera of TL patients and healthy subjects, besides the immune stimulation of peripheral blood mononuclear cells (PBMCs) collected from untreated and t...
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| Veröffentlicht in: | Parasitology 2019-03, Vol.146 (3), p.322-332 |
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| creator | Carvalho, Gerusa B. Costa, Lourena E. Lage, Daniela P. Ramos, Fernanda F. Santos, Thaís T. O. Ribeiro, Patrícia A. F. Dias, Daniel S. Salles, Beatriz C. S. Lima, Mariana P. Carvalho, Lívia M. Dias, Ana C. S. Alves, Patrícia T. Franklin, Michelle L. Silva, Renata A. M. Duarte, Mariana C. Menezes-Souza, Daniel Roatt, Bruno M. Chávez-Fumagalli, Miguel A. Goulart, Luiz Ricardo Teixeira, Antonio L. Coelho, Eduardo A. F. |
| description | In the current study, phage-exposed mimotopes as targets against tegumentary leishmaniasis (TL) were selected by means of bio-panning cycles employing sera of TL patients and healthy subjects, besides the immune stimulation of peripheral blood mononuclear cells (PBMCs) collected from untreated and treated TL patients and healthy subjects. The clones were evaluated regarding their specific interferon-γ (IFN-γ) and interleukin-4 (IL-4) production in the in vitro cultures, and selectivity and specificity values were calculated, and those presenting the best results were selected for the in vivo experiments. Two clones, namely A4 and A8, were identified and used in immunization protocols from BALB/c mice to protect against Leishmania amazonensis infection. Results showed a polarized Th1 response generated after vaccination, being based on significantly higher levels of IFN-γ, IL-2, IL-12, tumour necrosis factor-α (TNF-α) and granulocyte-macrophage colony-stimulating factor (GM-CSF); which were associated with lower production of specific IL-4, IL-10 and immunoglobulin G1 (IgG1) antibodies. Vaccinated mice presented significant reductions in the parasite load in the infected tissue and distinct organs, when compared with controls. In conclusion, we presented a strategy to identify new mimotopes able to induce Th1 response in PBMCs from TL patients and healthy subjects, and that were successfully used to protect against L. amazonensis infection. |
| doi_str_mv | 10.1017/S0031182018001403 |
| format | Article |
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O. ; Ribeiro, Patrícia A. F. ; Dias, Daniel S. ; Salles, Beatriz C. S. ; Lima, Mariana P. ; Carvalho, Lívia M. ; Dias, Ana C. S. ; Alves, Patrícia T. ; Franklin, Michelle L. ; Silva, Renata A. M. ; Duarte, Mariana C. ; Menezes-Souza, Daniel ; Roatt, Bruno M. ; Chávez-Fumagalli, Miguel A. ; Goulart, Luiz Ricardo ; Teixeira, Antonio L. ; Coelho, Eduardo A. F.</creator><creatorcontrib>Carvalho, Gerusa B. ; Costa, Lourena E. ; Lage, Daniela P. ; Ramos, Fernanda F. ; Santos, Thaís T. O. ; Ribeiro, Patrícia A. F. ; Dias, Daniel S. ; Salles, Beatriz C. S. ; Lima, Mariana P. ; Carvalho, Lívia M. ; Dias, Ana C. S. ; Alves, Patrícia T. ; Franklin, Michelle L. ; Silva, Renata A. M. ; Duarte, Mariana C. ; Menezes-Souza, Daniel ; Roatt, Bruno M. ; Chávez-Fumagalli, Miguel A. ; Goulart, Luiz Ricardo ; Teixeira, Antonio L. ; Coelho, Eduardo A. F.</creatorcontrib><description>In the current study, phage-exposed mimotopes as targets against tegumentary leishmaniasis (TL) were selected by means of bio-panning cycles employing sera of TL patients and healthy subjects, besides the immune stimulation of peripheral blood mononuclear cells (PBMCs) collected from untreated and treated TL patients and healthy subjects. The clones were evaluated regarding their specific interferon-γ (IFN-γ) and interleukin-4 (IL-4) production in the in vitro cultures, and selectivity and specificity values were calculated, and those presenting the best results were selected for the in vivo experiments. Two clones, namely A4 and A8, were identified and used in immunization protocols from BALB/c mice to protect against Leishmania amazonensis infection. Results showed a polarized Th1 response generated after vaccination, being based on significantly higher levels of IFN-γ, IL-2, IL-12, tumour necrosis factor-α (TNF-α) and granulocyte-macrophage colony-stimulating factor (GM-CSF); which were associated with lower production of specific IL-4, IL-10 and immunoglobulin G1 (IgG1) antibodies. Vaccinated mice presented significant reductions in the parasite load in the infected tissue and distinct organs, when compared with controls. In conclusion, we presented a strategy to identify new mimotopes able to induce Th1 response in PBMCs from TL patients and healthy subjects, and that were successfully used to protect against L. amazonensis infection.</description><identifier>ISSN: 0031-1820</identifier><identifier>EISSN: 1469-8161</identifier><identifier>DOI: 10.1017/S0031182018001403</identifier><identifier>PMID: 30198459</identifier><language>eng</language><publisher>Cambridge, UK: Cambridge University Press</publisher><subject>Adult ; Animals ; Antibodies ; Bacteriophages - immunology ; Candidates ; Cloning ; Colony-stimulating factor ; Experiments ; Female ; Granulocyte-macrophage colony stimulating factor ; High-Throughput Screening Assays ; Humans ; Immunization ; Immunoglobulin G ; Infections ; Interferon ; Interleukin 10 ; Interleukin 12 ; Interleukin 2 ; Interleukin 4 ; Laboratory animals ; Leishmania amazonensis ; Leishmania mexicana - immunology ; Leishmaniasis Vaccines - immunology ; Leishmaniasis, Cutaneous - immunology ; Leukocytes (mononuclear) ; Leukocytes, Mononuclear - immunology ; Lymphocytes ; Lymphocytes T ; Male ; Mice ; Mice, Inbred BALB C ; Middle Aged ; Organs ; Panning ; Parasites ; Parasitic diseases ; Patients ; Peptides ; Peripheral blood mononuclear cells ; Phages ; Proteins ; Selectivity ; T-Lymphocytes - immunology ; Tegumentary leishmaniasis ; Tumor necrosis factor-α ; Tumors ; Vaccination ; Vaccines ; Vector-borne diseases ; Young Adult ; γ-Interferon</subject><ispartof>Parasitology, 2019-03, Vol.146 (3), p.322-332</ispartof><rights>Copyright © Cambridge University Press 2018</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c421t-a9ff088cf255d788d498310fcef993d94e996b98c0bf499fabcc94701d10a4453</citedby><cites>FETCH-LOGICAL-c421t-a9ff088cf255d788d498310fcef993d94e996b98c0bf499fabcc94701d10a4453</cites><orcidid>0000-0002-6681-9014</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.cambridge.org/core/product/identifier/S0031182018001403/type/journal_article$$EHTML$$P50$$Gcambridge$$H</linktohtml><link.rule.ids>164,314,776,780,27901,27902,55603</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30198459$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Carvalho, Gerusa B.</creatorcontrib><creatorcontrib>Costa, Lourena E.</creatorcontrib><creatorcontrib>Lage, Daniela P.</creatorcontrib><creatorcontrib>Ramos, Fernanda F.</creatorcontrib><creatorcontrib>Santos, Thaís T. O.</creatorcontrib><creatorcontrib>Ribeiro, Patrícia A. F.</creatorcontrib><creatorcontrib>Dias, Daniel S.</creatorcontrib><creatorcontrib>Salles, Beatriz C. S.</creatorcontrib><creatorcontrib>Lima, Mariana P.</creatorcontrib><creatorcontrib>Carvalho, Lívia M.</creatorcontrib><creatorcontrib>Dias, Ana C. S.</creatorcontrib><creatorcontrib>Alves, Patrícia T.</creatorcontrib><creatorcontrib>Franklin, Michelle L.</creatorcontrib><creatorcontrib>Silva, Renata A. M.</creatorcontrib><creatorcontrib>Duarte, Mariana C.</creatorcontrib><creatorcontrib>Menezes-Souza, Daniel</creatorcontrib><creatorcontrib>Roatt, Bruno M.</creatorcontrib><creatorcontrib>Chávez-Fumagalli, Miguel A.</creatorcontrib><creatorcontrib>Goulart, Luiz Ricardo</creatorcontrib><creatorcontrib>Teixeira, Antonio L.</creatorcontrib><creatorcontrib>Coelho, Eduardo A. F.</creatorcontrib><title>High-through identification of T cell-specific phage-exposed mimotopes using PBMCs from tegumentary leishmaniasis patients and their use as vaccine candidates against Leishmania amazonensis infection</title><title>Parasitology</title><addtitle>Parasitology</addtitle><description>In the current study, phage-exposed mimotopes as targets against tegumentary leishmaniasis (TL) were selected by means of bio-panning cycles employing sera of TL patients and healthy subjects, besides the immune stimulation of peripheral blood mononuclear cells (PBMCs) collected from untreated and treated TL patients and healthy subjects. The clones were evaluated regarding their specific interferon-γ (IFN-γ) and interleukin-4 (IL-4) production in the in vitro cultures, and selectivity and specificity values were calculated, and those presenting the best results were selected for the in vivo experiments. Two clones, namely A4 and A8, were identified and used in immunization protocols from BALB/c mice to protect against Leishmania amazonensis infection. Results showed a polarized Th1 response generated after vaccination, being based on significantly higher levels of IFN-γ, IL-2, IL-12, tumour necrosis factor-α (TNF-α) and granulocyte-macrophage colony-stimulating factor (GM-CSF); which were associated with lower production of specific IL-4, IL-10 and immunoglobulin G1 (IgG1) antibodies. Vaccinated mice presented significant reductions in the parasite load in the infected tissue and distinct organs, when compared with controls. In conclusion, we presented a strategy to identify new mimotopes able to induce Th1 response in PBMCs from TL patients and healthy subjects, and that were successfully used to protect against L. amazonensis infection.</description><subject>Adult</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Bacteriophages - immunology</subject><subject>Candidates</subject><subject>Cloning</subject><subject>Colony-stimulating factor</subject><subject>Experiments</subject><subject>Female</subject><subject>Granulocyte-macrophage colony stimulating factor</subject><subject>High-Throughput Screening Assays</subject><subject>Humans</subject><subject>Immunization</subject><subject>Immunoglobulin G</subject><subject>Infections</subject><subject>Interferon</subject><subject>Interleukin 10</subject><subject>Interleukin 12</subject><subject>Interleukin 2</subject><subject>Interleukin 4</subject><subject>Laboratory animals</subject><subject>Leishmania amazonensis</subject><subject>Leishmania mexicana - immunology</subject><subject>Leishmaniasis Vaccines - immunology</subject><subject>Leishmaniasis, Cutaneous - immunology</subject><subject>Leukocytes (mononuclear)</subject><subject>Leukocytes, Mononuclear - immunology</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Middle Aged</subject><subject>Organs</subject><subject>Panning</subject><subject>Parasites</subject><subject>Parasitic diseases</subject><subject>Patients</subject><subject>Peptides</subject><subject>Peripheral blood mononuclear cells</subject><subject>Phages</subject><subject>Proteins</subject><subject>Selectivity</subject><subject>T-Lymphocytes - immunology</subject><subject>Tegumentary leishmaniasis</subject><subject>Tumor necrosis factor-α</subject><subject>Tumors</subject><subject>Vaccination</subject><subject>Vaccines</subject><subject>Vector-borne diseases</subject><subject>Young Adult</subject><subject>γ-Interferon</subject><issn>0031-1820</issn><issn>1469-8161</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kcGOFCEURYnROO3oB7gxJG7clEJBd8FSOzpj0kYTx3WFgkcVkwZKoMzoD_pbUpl2TDSuSN699_DyLkJPKXlJCe1efSaEUSpaQgUhlBN2D20o38lG0B29jzar3Kz6GXqU8zUhZMd27UN0xgiVgm_lBv28dOPUlCnFZZywMxCKs06r4mLA0eIrrOF4bPIMep3jeVIjNHAzxwwGe-djiTNkvGQXRvzpzYd9xjZFjwuMi680lb7jI7g8eRWcyi7jucKrkLEKBpcJXKppwCrjb0prFwDrqjijSuWqUbmQCz7cIbDy6kcMEFaWCxb0uutj9MCqY4Ynp_ccfXn39mp_2Rw-Xrzfvz40mre0NEpaS4TQtt1uTSeE4VIwSqwGKyUzkoOUu0EKTQbLpbRq0FryjlBDieJ8y87Ri1vunOLXBXLpvcvriVSAuOS-rcVISjsuqvX5X9bruKRQt6su0bGOdpJVF7116RRzTmD7OTlfr9ZT0q8t9_-0XDPPTuRl8GDuEr9rrQZ2gio_JGdG-PP3_7G_AG0Ntes</recordid><startdate>201903</startdate><enddate>201903</enddate><creator>Carvalho, Gerusa B.</creator><creator>Costa, Lourena E.</creator><creator>Lage, Daniela P.</creator><creator>Ramos, Fernanda F.</creator><creator>Santos, Thaís T. 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O. ; Ribeiro, Patrícia A. F. ; Dias, Daniel S. ; Salles, Beatriz C. S. ; Lima, Mariana P. ; Carvalho, Lívia M. ; Dias, Ana C. S. ; Alves, Patrícia T. ; Franklin, Michelle L. ; Silva, Renata A. M. ; Duarte, Mariana C. ; Menezes-Souza, Daniel ; Roatt, Bruno M. ; Chávez-Fumagalli, Miguel A. ; Goulart, Luiz Ricardo ; Teixeira, Antonio L. ; Coelho, Eduardo A. 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O.</au><au>Ribeiro, Patrícia A. F.</au><au>Dias, Daniel S.</au><au>Salles, Beatriz C. S.</au><au>Lima, Mariana P.</au><au>Carvalho, Lívia M.</au><au>Dias, Ana C. S.</au><au>Alves, Patrícia T.</au><au>Franklin, Michelle L.</au><au>Silva, Renata A. M.</au><au>Duarte, Mariana C.</au><au>Menezes-Souza, Daniel</au><au>Roatt, Bruno M.</au><au>Chávez-Fumagalli, Miguel A.</au><au>Goulart, Luiz Ricardo</au><au>Teixeira, Antonio L.</au><au>Coelho, Eduardo A. F.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>High-through identification of T cell-specific phage-exposed mimotopes using PBMCs from tegumentary leishmaniasis patients and their use as vaccine candidates against Leishmania amazonensis infection</atitle><jtitle>Parasitology</jtitle><addtitle>Parasitology</addtitle><date>2019-03</date><risdate>2019</risdate><volume>146</volume><issue>3</issue><spage>322</spage><epage>332</epage><pages>322-332</pages><issn>0031-1820</issn><eissn>1469-8161</eissn><abstract>In the current study, phage-exposed mimotopes as targets against tegumentary leishmaniasis (TL) were selected by means of bio-panning cycles employing sera of TL patients and healthy subjects, besides the immune stimulation of peripheral blood mononuclear cells (PBMCs) collected from untreated and treated TL patients and healthy subjects. The clones were evaluated regarding their specific interferon-γ (IFN-γ) and interleukin-4 (IL-4) production in the in vitro cultures, and selectivity and specificity values were calculated, and those presenting the best results were selected for the in vivo experiments. Two clones, namely A4 and A8, were identified and used in immunization protocols from BALB/c mice to protect against Leishmania amazonensis infection. Results showed a polarized Th1 response generated after vaccination, being based on significantly higher levels of IFN-γ, IL-2, IL-12, tumour necrosis factor-α (TNF-α) and granulocyte-macrophage colony-stimulating factor (GM-CSF); which were associated with lower production of specific IL-4, IL-10 and immunoglobulin G1 (IgG1) antibodies. Vaccinated mice presented significant reductions in the parasite load in the infected tissue and distinct organs, when compared with controls. In conclusion, we presented a strategy to identify new mimotopes able to induce Th1 response in PBMCs from TL patients and healthy subjects, and that were successfully used to protect against L. amazonensis infection.</abstract><cop>Cambridge, UK</cop><pub>Cambridge University Press</pub><pmid>30198459</pmid><doi>10.1017/S0031182018001403</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-6681-9014</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0031-1820 |
| ispartof | Parasitology, 2019-03, Vol.146 (3), p.322-332 |
| issn | 0031-1820 1469-8161 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2101911748 |
| source | Cambridge Journals Online; MEDLINE |
| subjects | Adult Animals Antibodies Bacteriophages - immunology Candidates Cloning Colony-stimulating factor Experiments Female Granulocyte-macrophage colony stimulating factor High-Throughput Screening Assays Humans Immunization Immunoglobulin G Infections Interferon Interleukin 10 Interleukin 12 Interleukin 2 Interleukin 4 Laboratory animals Leishmania amazonensis Leishmania mexicana - immunology Leishmaniasis Vaccines - immunology Leishmaniasis, Cutaneous - immunology Leukocytes (mononuclear) Leukocytes, Mononuclear - immunology Lymphocytes Lymphocytes T Male Mice Mice, Inbred BALB C Middle Aged Organs Panning Parasites Parasitic diseases Patients Peptides Peripheral blood mononuclear cells Phages Proteins Selectivity T-Lymphocytes - immunology Tegumentary leishmaniasis Tumor necrosis factor-α Tumors Vaccination Vaccines Vector-borne diseases Young Adult γ-Interferon |
| title | High-through identification of T cell-specific phage-exposed mimotopes using PBMCs from tegumentary leishmaniasis patients and their use as vaccine candidates against Leishmania amazonensis infection |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-07T15%3A17%3A58IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=High-through%20identification%20of%20T%20cell-specific%20phage-exposed%20mimotopes%20using%20PBMCs%20from%20tegumentary%20leishmaniasis%20patients%20and%20their%20use%20as%20vaccine%20candidates%20against%20Leishmania%20amazonensis%20infection&rft.jtitle=Parasitology&rft.au=Carvalho,%20Gerusa%20B.&rft.date=2019-03&rft.volume=146&rft.issue=3&rft.spage=322&rft.epage=332&rft.pages=322-332&rft.issn=0031-1820&rft.eissn=1469-8161&rft_id=info:doi/10.1017/S0031182018001403&rft_dat=%3Cproquest_cross%3E2187371793%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2187371793&rft_id=info:pmid/30198459&rft_cupid=10_1017_S0031182018001403&rfr_iscdi=true |