Engineering a single-chain antibody against Trypanosoma cruzi metacyclic trypomastigotes to block cell invasion
Trypanosoma cruzi is a flagellate protozoan pathogen that causes Chagas disease. Currently there is no preventive treatment and the efficiency of the two drugs available is limited to the acute phase. Therefore, there is an unmet need for innovative tools to block transmission in endemic areas. In t...
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| creator | Demeu, Lara Maria Kalempa Soares, Rodrigo Jahn Miranda, Juliana Severo Pacheco-Lugo, Lisandro A Oliveira, Kelin Gonçalves Cortez Plaza, Cristian Andrés Billiald, Philippe Ferreira de Moura, Juliana Yoshida, Nobuko Alvarenga, Larissa Magalhães DaRocha, Wanderson Duarte |
| description | Trypanosoma cruzi is a flagellate protozoan pathogen that causes Chagas disease. Currently there is no preventive treatment and the efficiency of the two drugs available is limited to the acute phase. Therefore, there is an unmet need for innovative tools to block transmission in endemic areas. In this study, we engineered a novel recombinant molecule able to adhere to the T. cruzi surface, termed scFv-10D8, that consists of a single-chain variable fragment (scFv) derived from mAb-10D8 that targets gp35/50. The synthetic gene encoding scFv-10D8 was cloned and fused to a 6×His tag and expressed in a prokaryotic expression system. Total periplasmic or 6xHis tag affinity-purified fractions of scFv-10D8 retained the capacity to bind to gp35/50, as shown by Western blot analyses. Pre-incubation of metacyclic trypomastigotes with scFv-10D8 showed a remarkable reduction in cell invasion capacity. Our results suggest that scFv-10D8 can be used in a paratransgenic approach to target parasites in insect vectors, avoiding dissemination of infective forms. Such advances in the development of this functional molecule will surely prompt the improvement of alternative strategies to control Chagas disease by targeting mammalian host stages. |
| doi_str_mv | 10.1371/journal.pone.0223773 |
| format | Article |
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Currently there is no preventive treatment and the efficiency of the two drugs available is limited to the acute phase. Therefore, there is an unmet need for innovative tools to block transmission in endemic areas. In this study, we engineered a novel recombinant molecule able to adhere to the T. cruzi surface, termed scFv-10D8, that consists of a single-chain variable fragment (scFv) derived from mAb-10D8 that targets gp35/50. The synthetic gene encoding scFv-10D8 was cloned and fused to a 6×His tag and expressed in a prokaryotic expression system. Total periplasmic or 6xHis tag affinity-purified fractions of scFv-10D8 retained the capacity to bind to gp35/50, as shown by Western blot analyses. Pre-incubation of metacyclic trypomastigotes with scFv-10D8 showed a remarkable reduction in cell invasion capacity. Our results suggest that scFv-10D8 can be used in a paratransgenic approach to target parasites in insect vectors, avoiding dissemination of infective forms. Such advances in the development of this functional molecule will surely prompt the improvement of alternative strategies to control Chagas disease by targeting mammalian host stages.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0223773</identifier><identifier>PMID: 31618282</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Antibodies ; Antibodies, Protozoan - genetics ; Antibodies, Protozoan - pharmacology ; Antigens, Protozoan - immunology ; Biology and Life Sciences ; Cell Line ; Chagas disease ; Chagas Disease - drug therapy ; Chagas Disease - parasitology ; Chagas Disease - prevention & control ; Chains ; Cloning ; Disease ; Disease control ; HeLa Cells ; Human health and pathology ; Humans ; Immunoglobulins ; Immunology ; Incubation ; Infectious diseases ; Insects ; Life Sciences ; Medical treatment ; Medicine and Health Sciences ; Microbiology and Parasitology ; Monoclonal antibodies ; Nanoparticles ; Parasites ; Parasitology ; Peptides ; Pharmaceuticals ; Protein Engineering - methods ; Proteins ; Protozoa ; Recombinant Proteins - genetics ; Recombinant Proteins - pharmacology ; Research and Analysis Methods ; Single-Chain Antibodies - genetics ; Single-Chain Antibodies - pharmacology ; Trypanosoma cruzi ; Trypanosoma cruzi - drug effects ; Trypanosoma cruzi - immunology ; Trypomastigotes ; Vaccinology ; Vector-borne diseases ; Vectors</subject><ispartof>PloS one, 2019, Vol.14 (10), p.e0223773-e0223773</ispartof><rights>2019 Demeu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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Currently there is no preventive treatment and the efficiency of the two drugs available is limited to the acute phase. Therefore, there is an unmet need for innovative tools to block transmission in endemic areas. In this study, we engineered a novel recombinant molecule able to adhere to the T. cruzi surface, termed scFv-10D8, that consists of a single-chain variable fragment (scFv) derived from mAb-10D8 that targets gp35/50. The synthetic gene encoding scFv-10D8 was cloned and fused to a 6×His tag and expressed in a prokaryotic expression system. Total periplasmic or 6xHis tag affinity-purified fractions of scFv-10D8 retained the capacity to bind to gp35/50, as shown by Western blot analyses. Pre-incubation of metacyclic trypomastigotes with scFv-10D8 showed a remarkable reduction in cell invasion capacity. Our results suggest that scFv-10D8 can be used in a paratransgenic approach to target parasites in insect vectors, avoiding dissemination of infective forms. Such advances in the development of this functional molecule will surely prompt the improvement of alternative strategies to control Chagas disease by targeting mammalian host stages.</description><subject>Antibodies</subject><subject>Antibodies, Protozoan - genetics</subject><subject>Antibodies, Protozoan - pharmacology</subject><subject>Antigens, Protozoan - immunology</subject><subject>Biology and Life Sciences</subject><subject>Cell Line</subject><subject>Chagas disease</subject><subject>Chagas Disease - drug therapy</subject><subject>Chagas Disease - parasitology</subject><subject>Chagas Disease - prevention & control</subject><subject>Chains</subject><subject>Cloning</subject><subject>Disease</subject><subject>Disease control</subject><subject>HeLa Cells</subject><subject>Human health and pathology</subject><subject>Humans</subject><subject>Immunoglobulins</subject><subject>Immunology</subject><subject>Incubation</subject><subject>Infectious diseases</subject><subject>Insects</subject><subject>Life Sciences</subject><subject>Medical treatment</subject><subject>Medicine and Health Sciences</subject><subject>Microbiology and Parasitology</subject><subject>Monoclonal antibodies</subject><subject>Nanoparticles</subject><subject>Parasites</subject><subject>Parasitology</subject><subject>Peptides</subject><subject>Pharmaceuticals</subject><subject>Protein Engineering - methods</subject><subject>Proteins</subject><subject>Protozoa</subject><subject>Recombinant Proteins - genetics</subject><subject>Recombinant Proteins - pharmacology</subject><subject>Research and Analysis Methods</subject><subject>Single-Chain Antibodies - genetics</subject><subject>Single-Chain Antibodies - pharmacology</subject><subject>Trypanosoma cruzi</subject><subject>Trypanosoma cruzi - drug effects</subject><subject>Trypanosoma cruzi - immunology</subject><subject>Trypomastigotes</subject><subject>Vaccinology</subject><subject>Vector-borne diseases</subject><subject>Vectors</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNptUk1rGzEQXUpL89H-g9IKeikFu_pa7eoSCCFtAoZe0rOY1c6u5e5KriQb3F_fdeyEJPQ0kua9N5rHK4oPjM6ZqNi3VdhED8N8HTzOKeeiqsSr4pRpwWeKU_H6yfmkOEtpRWkpaqXeFieCKVbzmp8W4dr3ziNG53sCJE1lwJldgvMEfHZNaHcE-umaMrmLuzX4kMIIxMbNX0dGzGB3dnCW5Kk5NVJ2fciYSA6kGYL9TSwOA3F-C8kF_65408GQ8P2xnhe_vl_fXd3MFj9_3F5dLma2VCzPuO2YbnQjJW8VoxJEq3UrKQhUyJRqsFQUrWw11rrV0AjKBJRQyopKwVpxXnw66K6HkMzRq2S4oHs_dCUmxO0B0QZYmXV0I8SdCeDM_UOIvYGYnR3QdHyaLm1nK9vKRpa1QMmUhg5RV1bBpHVxnLZpRmwt-hxheCb6vOPd0vRha1SlS6n4JPD1ILB8Qbu5XJjRL72hQknGynLLJvCX47QY_mwwZTO6tHcZPIbNYUmpS13vl_z8Avp_K-QBZWNIKWL3-AVGzT5sDyyzD5s5hm2ifXy69SPpIV3iH8JJ1KA</recordid><startdate>2019</startdate><enddate>2019</enddate><creator>Demeu, Lara Maria Kalempa</creator><creator>Soares, Rodrigo Jahn</creator><creator>Miranda, Juliana Severo</creator><creator>Pacheco-Lugo, Lisandro A</creator><creator>Oliveira, Kelin Gonçalves</creator><creator>Cortez Plaza, Cristian Andrés</creator><creator>Billiald, Philippe</creator><creator>Ferreira de Moura, Juliana</creator><creator>Yoshida, Nobuko</creator><creator>Alvarenga, Larissa Magalhães</creator><creator>DaRocha, Wanderson Duarte</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>1XC</scope><scope>VOOES</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-8722-5143</orcidid></search><sort><creationdate>2019</creationdate><title>Engineering a single-chain antibody against Trypanosoma cruzi metacyclic trypomastigotes to block cell invasion</title><author>Demeu, Lara Maria Kalempa ; Soares, Rodrigo Jahn ; Miranda, Juliana Severo ; Pacheco-Lugo, Lisandro A ; Oliveira, Kelin Gonçalves ; Cortez Plaza, Cristian Andrés ; Billiald, Philippe ; Ferreira de Moura, Juliana ; Yoshida, Nobuko ; Alvarenga, Larissa Magalhães ; DaRocha, Wanderson Duarte</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c561t-2cf19b9b442d6104a3d99d40a3e6e166be560ec4d9e89d9ab3013a5a5470431d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Antibodies</topic><topic>Antibodies, Protozoan - 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Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Demeu, Lara Maria Kalempa</au><au>Soares, Rodrigo Jahn</au><au>Miranda, Juliana Severo</au><au>Pacheco-Lugo, Lisandro A</au><au>Oliveira, Kelin Gonçalves</au><au>Cortez Plaza, Cristian Andrés</au><au>Billiald, Philippe</au><au>Ferreira de Moura, Juliana</au><au>Yoshida, Nobuko</au><au>Alvarenga, Larissa Magalhães</au><au>DaRocha, Wanderson Duarte</au><au>Di Noia, Javier Marcelo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Engineering a single-chain antibody against Trypanosoma cruzi metacyclic trypomastigotes to block cell invasion</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2019</date><risdate>2019</risdate><volume>14</volume><issue>10</issue><spage>e0223773</spage><epage>e0223773</epage><pages>e0223773-e0223773</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Trypanosoma cruzi is a flagellate protozoan pathogen that causes Chagas disease. Currently there is no preventive treatment and the efficiency of the two drugs available is limited to the acute phase. Therefore, there is an unmet need for innovative tools to block transmission in endemic areas. In this study, we engineered a novel recombinant molecule able to adhere to the T. cruzi surface, termed scFv-10D8, that consists of a single-chain variable fragment (scFv) derived from mAb-10D8 that targets gp35/50. The synthetic gene encoding scFv-10D8 was cloned and fused to a 6×His tag and expressed in a prokaryotic expression system. Total periplasmic or 6xHis tag affinity-purified fractions of scFv-10D8 retained the capacity to bind to gp35/50, as shown by Western blot analyses. Pre-incubation of metacyclic trypomastigotes with scFv-10D8 showed a remarkable reduction in cell invasion capacity. Our results suggest that scFv-10D8 can be used in a paratransgenic approach to target parasites in insect vectors, avoiding dissemination of infective forms. Such advances in the development of this functional molecule will surely prompt the improvement of alternative strategies to control Chagas disease by targeting mammalian host stages.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>31618282</pmid><doi>10.1371/journal.pone.0223773</doi><orcidid>https://orcid.org/0000-0002-8722-5143</orcidid><oa>free_for_read</oa></addata></record> |
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| language | eng |
| recordid | cdi_plos_journals_2306203973 |
| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Antibodies Antibodies, Protozoan - genetics Antibodies, Protozoan - pharmacology Antigens, Protozoan - immunology Biology and Life Sciences Cell Line Chagas disease Chagas Disease - drug therapy Chagas Disease - parasitology Chagas Disease - prevention & control Chains Cloning Disease Disease control HeLa Cells Human health and pathology Humans Immunoglobulins Immunology Incubation Infectious diseases Insects Life Sciences Medical treatment Medicine and Health Sciences Microbiology and Parasitology Monoclonal antibodies Nanoparticles Parasites Parasitology Peptides Pharmaceuticals Protein Engineering - methods Proteins Protozoa Recombinant Proteins - genetics Recombinant Proteins - pharmacology Research and Analysis Methods Single-Chain Antibodies - genetics Single-Chain Antibodies - pharmacology Trypanosoma cruzi Trypanosoma cruzi - drug effects Trypanosoma cruzi - immunology Trypomastigotes Vaccinology Vector-borne diseases Vectors |
| title | Engineering a single-chain antibody against Trypanosoma cruzi metacyclic trypomastigotes to block cell invasion |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-31T19%3A59%3A20IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Engineering%20a%20single-chain%20antibody%20against%20Trypanosoma%20cruzi%20metacyclic%20trypomastigotes%20to%20block%20cell%20invasion&rft.jtitle=PloS%20one&rft.au=Demeu,%20Lara%20Maria%20Kalempa&rft.date=2019&rft.volume=14&rft.issue=10&rft.spage=e0223773&rft.epage=e0223773&rft.pages=e0223773-e0223773&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0223773&rft_dat=%3Cproquest_plos_%3E2306495983%3C/proquest_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2306203973&rft_id=info:pmid/31618282&rft_doaj_id=oai_doaj_org_article_f2d994cfc7cd4b4583e4169afee97c6a&rfr_iscdi=true |