Oral delivery of the Sj23LHD-GST antigen by Salmonella typhimurium type III secretion system protects against Schistosoma japonicum infection in mice
Schistosomiasis japonica is a zoonotic parasitic disease and oral vaccine delivery system would be benefit for prevention of this disease. Although attenuated salmonella has been used as an antigen expression vector for oral vaccine development, the membrane-bound vacuoles in which bacteria reside h...
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| description | Schistosomiasis japonica is a zoonotic parasitic disease and oral vaccine delivery system would be benefit for prevention of this disease. Although attenuated salmonella has been used as an antigen expression vector for oral vaccine development, the membrane-bound vacuoles in which bacteria reside hinders the presentation of expressed heterologous antigens to the major histocompatibility complex (MHC) molecules. The present work used an attenuated Salmonella typhimurium strain VNP20009 to secretory expression of Sj23LHDGST bivalent antigen from Schistosoma japonicum and tested the protective efficacy against S. japonicum infection in orally immunized mice.
Promoters (nirB or pagC) were used to express the antigen (Sj23LHDGST) and the Salmonella type III or α-hemolysin secretion system was employed to secrete it. The immunoblotting analysis and fluorescent microscopy revealed that the antigen was effectively expressed and delivered to the cytosol of macrophages in vitro. Among recombinant vaccine strains, an engineered VNP20009 which expressed the antigen by nirB promoter and secreted it through type III secretion system (nirB-sopE(1-104)-Sj23LHD-GST) efficiently protected against S. japonicum infection in a mouse model. This strain elicited a predominantly IgG(2a) antibody response and a markedly increase in the production of IL-12 and IFN-γ. The flow cytometric analysis demonstrated that this strain caused T cell activation as evidenced by significantly increased expression of CD44 and CD69.
Oral delivery of antigen by nirB-driven Salmonella typhimurium type III secretion system is a novel, safe, inexpensive, efficient and convenient approach for schistosome vaccine development. |
| doi_str_mv | 10.1371/journal.pntd.0001313 |
| format | Article |
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Promoters (nirB or pagC) were used to express the antigen (Sj23LHDGST) and the Salmonella type III or α-hemolysin secretion system was employed to secrete it. The immunoblotting analysis and fluorescent microscopy revealed that the antigen was effectively expressed and delivered to the cytosol of macrophages in vitro. Among recombinant vaccine strains, an engineered VNP20009 which expressed the antigen by nirB promoter and secreted it through type III secretion system (nirB-sopE(1-104)-Sj23LHD-GST) efficiently protected against S. japonicum infection in a mouse model. This strain elicited a predominantly IgG(2a) antibody response and a markedly increase in the production of IL-12 and IFN-γ. The flow cytometric analysis demonstrated that this strain caused T cell activation as evidenced by significantly increased expression of CD44 and CD69.
Oral delivery of antigen by nirB-driven Salmonella typhimurium type III secretion system is a novel, safe, inexpensive, efficient and convenient approach for schistosome vaccine development.</description><identifier>ISSN: 1935-2735</identifier><identifier>ISSN: 1935-2727</identifier><identifier>EISSN: 1935-2735</identifier><identifier>DOI: 10.1371/journal.pntd.0001313</identifier><identifier>PMID: 21909450</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Administration, Oral ; Analysis ; Animals ; Antibodies, Helminth - blood ; Antigens ; Antigens, Helminth - genetics ; Antigens, Helminth - immunology ; Bacterial Vaccines - administration & dosage ; Bacterial Vaccines - adverse effects ; Bacterial Vaccines - genetics ; Bacterial Vaccines - immunology ; Care and treatment ; Clinical trials ; Disease Models, Animal ; Feces - parasitology ; Female ; Genetic Vectors ; Granuloma - pathology ; Granuloma - prevention & control ; Health aspects ; Immunoglobulin G - blood ; Infections ; Interferon-gamma - secretion ; Interleukin-12 - secretion ; Macrophages - immunology ; Medicine ; Mice ; Mice, Inbred BALB C ; Parasite Egg Count ; Parasitic diseases ; Proteins ; Salmonella ; Salmonella typhimurium ; Salmonella typhimurium - genetics ; Schistosoma japonicum ; Schistosoma japonicum - genetics ; Schistosoma japonicum - immunology ; Schistosomiasis ; Schistosomiasis japonica - immunology ; Schistosomiasis japonica - pathology ; Schistosomiasis japonica - prevention & control ; Tropical diseases ; Vaccination - methods ; Vaccines ; Vaccines, Synthetic - administration & dosage ; Vaccines, Synthetic - adverse effects ; Vaccines, Synthetic - genetics ; Vaccines, Synthetic - immunology ; Zoonoses</subject><ispartof>PLoS neglected tropical diseases, 2011-09, Vol.5 (9), p.e1313</ispartof><rights>COPYRIGHT 2011 Public Library of Science</rights><rights>2011 Chen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Chen G, Dai Y, Chen J, Wang X, Tang B, et al. (2011) Oral Delivery of the Sj23LHD-GST Antigen by Salmonella typhimurium Type III Secretion System Protects against Schistosoma japonicum Infection in Mice. PLoS Negl Trop Dis 5(9): e1313. doi:10.1371/journal.pntd.0001313</rights><rights>Chen et al. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c655t-9151b28421357d603e0fe23e541d4f3ebeab466de24c2d910d5eb129f313bb363</citedby><cites>FETCH-LOGICAL-c655t-9151b28421357d603e0fe23e541d4f3ebeab466de24c2d910d5eb129f313bb363</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3167783/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3167783/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27903,27904,53769,53771,79346,79347</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21909450$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Dalton, John Pius</contributor><creatorcontrib>Chen, Guo</creatorcontrib><creatorcontrib>Dai, Yang</creatorcontrib><creatorcontrib>Chen, Jianxiang</creatorcontrib><creatorcontrib>Wang, Xiaoting</creatorcontrib><creatorcontrib>Tang, Bo</creatorcontrib><creatorcontrib>Zhu, Yinchang</creatorcontrib><creatorcontrib>Hua, Zichun</creatorcontrib><title>Oral delivery of the Sj23LHD-GST antigen by Salmonella typhimurium type III secretion system protects against Schistosoma japonicum infection in mice</title><title>PLoS neglected tropical diseases</title><addtitle>PLoS Negl Trop Dis</addtitle><description>Schistosomiasis japonica is a zoonotic parasitic disease and oral vaccine delivery system would be benefit for prevention of this disease. Although attenuated salmonella has been used as an antigen expression vector for oral vaccine development, the membrane-bound vacuoles in which bacteria reside hinders the presentation of expressed heterologous antigens to the major histocompatibility complex (MHC) molecules. The present work used an attenuated Salmonella typhimurium strain VNP20009 to secretory expression of Sj23LHDGST bivalent antigen from Schistosoma japonicum and tested the protective efficacy against S. japonicum infection in orally immunized mice.
Promoters (nirB or pagC) were used to express the antigen (Sj23LHDGST) and the Salmonella type III or α-hemolysin secretion system was employed to secrete it. The immunoblotting analysis and fluorescent microscopy revealed that the antigen was effectively expressed and delivered to the cytosol of macrophages in vitro. Among recombinant vaccine strains, an engineered VNP20009 which expressed the antigen by nirB promoter and secreted it through type III secretion system (nirB-sopE(1-104)-Sj23LHD-GST) efficiently protected against S. japonicum infection in a mouse model. This strain elicited a predominantly IgG(2a) antibody response and a markedly increase in the production of IL-12 and IFN-γ. The flow cytometric analysis demonstrated that this strain caused T cell activation as evidenced by significantly increased expression of CD44 and CD69.
Oral delivery of antigen by nirB-driven Salmonella typhimurium type III secretion system is a novel, safe, inexpensive, efficient and convenient approach for schistosome vaccine development.</description><subject>Administration, Oral</subject><subject>Analysis</subject><subject>Animals</subject><subject>Antibodies, Helminth - blood</subject><subject>Antigens</subject><subject>Antigens, Helminth - genetics</subject><subject>Antigens, Helminth - immunology</subject><subject>Bacterial Vaccines - administration & dosage</subject><subject>Bacterial Vaccines - adverse effects</subject><subject>Bacterial Vaccines - genetics</subject><subject>Bacterial Vaccines - immunology</subject><subject>Care and treatment</subject><subject>Clinical trials</subject><subject>Disease Models, Animal</subject><subject>Feces - parasitology</subject><subject>Female</subject><subject>Genetic Vectors</subject><subject>Granuloma - pathology</subject><subject>Granuloma - prevention & control</subject><subject>Health aspects</subject><subject>Immunoglobulin G - blood</subject><subject>Infections</subject><subject>Interferon-gamma - secretion</subject><subject>Interleukin-12 - secretion</subject><subject>Macrophages - immunology</subject><subject>Medicine</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Parasite Egg Count</subject><subject>Parasitic diseases</subject><subject>Proteins</subject><subject>Salmonella</subject><subject>Salmonella typhimurium</subject><subject>Salmonella typhimurium - genetics</subject><subject>Schistosoma japonicum</subject><subject>Schistosoma japonicum - genetics</subject><subject>Schistosoma japonicum - immunology</subject><subject>Schistosomiasis</subject><subject>Schistosomiasis japonica - immunology</subject><subject>Schistosomiasis japonica - pathology</subject><subject>Schistosomiasis japonica - prevention & control</subject><subject>Tropical diseases</subject><subject>Vaccination - methods</subject><subject>Vaccines</subject><subject>Vaccines, Synthetic - administration & dosage</subject><subject>Vaccines, Synthetic - 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Although attenuated salmonella has been used as an antigen expression vector for oral vaccine development, the membrane-bound vacuoles in which bacteria reside hinders the presentation of expressed heterologous antigens to the major histocompatibility complex (MHC) molecules. The present work used an attenuated Salmonella typhimurium strain VNP20009 to secretory expression of Sj23LHDGST bivalent antigen from Schistosoma japonicum and tested the protective efficacy against S. japonicum infection in orally immunized mice.
Promoters (nirB or pagC) were used to express the antigen (Sj23LHDGST) and the Salmonella type III or α-hemolysin secretion system was employed to secrete it. The immunoblotting analysis and fluorescent microscopy revealed that the antigen was effectively expressed and delivered to the cytosol of macrophages in vitro. Among recombinant vaccine strains, an engineered VNP20009 which expressed the antigen by nirB promoter and secreted it through type III secretion system (nirB-sopE(1-104)-Sj23LHD-GST) efficiently protected against S. japonicum infection in a mouse model. This strain elicited a predominantly IgG(2a) antibody response and a markedly increase in the production of IL-12 and IFN-γ. The flow cytometric analysis demonstrated that this strain caused T cell activation as evidenced by significantly increased expression of CD44 and CD69.
Oral delivery of antigen by nirB-driven Salmonella typhimurium type III secretion system is a novel, safe, inexpensive, efficient and convenient approach for schistosome vaccine development.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>21909450</pmid><doi>10.1371/journal.pntd.0001313</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1935-2735 |
| ispartof | PLoS neglected tropical diseases, 2011-09, Vol.5 (9), p.e1313 |
| issn | 1935-2735 1935-2727 1935-2735 |
| language | eng |
| recordid | cdi_plos_journals_1288113328 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; PubMed Central Open Access; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Administration, Oral Analysis Animals Antibodies, Helminth - blood Antigens Antigens, Helminth - genetics Antigens, Helminth - immunology Bacterial Vaccines - administration & dosage Bacterial Vaccines - adverse effects Bacterial Vaccines - genetics Bacterial Vaccines - immunology Care and treatment Clinical trials Disease Models, Animal Feces - parasitology Female Genetic Vectors Granuloma - pathology Granuloma - prevention & control Health aspects Immunoglobulin G - blood Infections Interferon-gamma - secretion Interleukin-12 - secretion Macrophages - immunology Medicine Mice Mice, Inbred BALB C Parasite Egg Count Parasitic diseases Proteins Salmonella Salmonella typhimurium Salmonella typhimurium - genetics Schistosoma japonicum Schistosoma japonicum - genetics Schistosoma japonicum - immunology Schistosomiasis Schistosomiasis japonica - immunology Schistosomiasis japonica - pathology Schistosomiasis japonica - prevention & control Tropical diseases Vaccination - methods Vaccines Vaccines, Synthetic - administration & dosage Vaccines, Synthetic - adverse effects Vaccines, Synthetic - genetics Vaccines, Synthetic - immunology Zoonoses |
| title | Oral delivery of the Sj23LHD-GST antigen by Salmonella typhimurium type III secretion system protects against Schistosoma japonicum infection in mice |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-24T09%3A36%3A54IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Oral%20delivery%20of%20the%20Sj23LHD-GST%20antigen%20by%20Salmonella%20typhimurium%20type%20III%20secretion%20system%20protects%20against%20Schistosoma%20japonicum%20infection%20in%20mice&rft.jtitle=PLoS%20neglected%20tropical%20diseases&rft.au=Chen,%20Guo&rft.date=2011-09-01&rft.volume=5&rft.issue=9&rft.spage=e1313&rft.pages=e1313-&rft.issn=1935-2735&rft.eissn=1935-2735&rft_id=info:doi/10.1371/journal.pntd.0001313&rft_dat=%3Cgale_plos_%3EA269531356%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1288113328&rft_id=info:pmid/21909450&rft_galeid=A269531356&rft_doaj_id=oai_doaj_org_article_278ee89b07af47458a4e32524689edc6&rfr_iscdi=true |