Intranasal administration of a synthetic lipopeptide without adjuvant induces systemic immune responses
Summary Parenteral injection of a lipopeptide containing a human leucocyte antigen (HLA)‐A*0201‐restricted cytotoxic T‐lymphocyte (CTL) epitope from the human cytomegalovirus (HCMV) immunodominant matrix protein pp65 efficiently induces systemic CTL responses in HLA‐A*0201 transgenic mice. In this s...
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| Veröffentlicht in: | Immunology 2002-05, Vol.106 (1), p.113-121 |
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| creator | BenMohamed, Lbachir Krishnan, Radhika Auge, Catherine Primus, James F. Diamond, Don J. |
| description | Summary
Parenteral injection of a lipopeptide containing a human leucocyte antigen (HLA)‐A*0201‐restricted cytotoxic T‐lymphocyte (CTL) epitope from the human cytomegalovirus (HCMV) immunodominant matrix protein pp65 efficiently induces systemic CTL responses in HLA‐A*0201 transgenic mice. In this study, we demonstrate that intranasal (i.n.) administration of this lipopeptide, covalently linked to a universal T helper (Th) epitope (PADRE), also induces potent systemic CTL responses. Immune responses were substantially reduced when the unlipidated peptide analogue was used (P |
| doi_str_mv | 10.1046/j.1365-2567.2002.01396.x |
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Parenteral injection of a lipopeptide containing a human leucocyte antigen (HLA)‐A*0201‐restricted cytotoxic T‐lymphocyte (CTL) epitope from the human cytomegalovirus (HCMV) immunodominant matrix protein pp65 efficiently induces systemic CTL responses in HLA‐A*0201 transgenic mice. In this study, we demonstrate that intranasal (i.n.) administration of this lipopeptide, covalently linked to a universal T helper (Th) epitope (PADRE), also induces potent systemic CTL responses. Immune responses were substantially reduced when the unlipidated peptide analogue was used (P<0·01). The induced CTL were CD8+, major histocompatibility complex (MHC) class I‐restricted and CMV specific. Moreover, i.n. administration of this lipidated peptide elicited both systemic and local mucosal CD4+ T‐cell proliferative responses, as well as antigen‐specific delayed type hypersensitivity (DTH) immune responses. In contrast, mice receiving the unlipidated peptide analogue developed substantially reduced Th or DTH responses (P<0·05). These results highlight the usefulness and potential of lipopeptides delivered via mucosal routes as painless, safe, and non‐invasive vaccines.</description><identifier>ISSN: 0019-2805</identifier><identifier>EISSN: 1365-2567</identifier><identifier>DOI: 10.1046/j.1365-2567.2002.01396.x</identifier><identifier>PMID: 11972639</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Science Ltd</publisher><subject>Administration, Intranasal ; Animals ; Antigens, Viral - immunology ; CD4-Positive T-Lymphocytes - immunology ; Cell Line ; Cytomegalovirus Vaccines - immunology ; HLA-A Antigens - immunology ; HLA-A2 Antigen ; Humans ; Hypersensitivity, Delayed - immunology ; Immunity, Mucosal ; Immunization - methods ; Lymphocyte Activation ; Malaria Vaccines - immunology ; Mice ; Mice, Transgenic ; Original ; Phosphoproteins - immunology ; T-Lymphocytes, Cytotoxic - immunology ; Viral Matrix Proteins - immunology</subject><ispartof>Immunology, 2002-05, Vol.106 (1), p.113-121</ispartof><rights>Copyright Blackwell Scientific Publications Ltd. May 2002</rights><rights>2002 Blackwell Science Ltd 2002</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5946-1f9f54d990bb7a401bd1ab24200d6eb4c2129fa44a1418413a9a62b384fb43293</citedby><cites>FETCH-LOGICAL-c5946-1f9f54d990bb7a401bd1ab24200d6eb4c2129fa44a1418413a9a62b384fb43293</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/PMC1782698/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1782698/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,1417,1433,27924,27925,45574,45575,46409,46833,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11972639$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>BenMohamed, Lbachir</creatorcontrib><creatorcontrib>Krishnan, Radhika</creatorcontrib><creatorcontrib>Auge, Catherine</creatorcontrib><creatorcontrib>Primus, James F.</creatorcontrib><creatorcontrib>Diamond, Don J.</creatorcontrib><title>Intranasal administration of a synthetic lipopeptide without adjuvant induces systemic immune responses</title><title>Immunology</title><addtitle>Immunology</addtitle><description>Summary
Parenteral injection of a lipopeptide containing a human leucocyte antigen (HLA)‐A*0201‐restricted cytotoxic T‐lymphocyte (CTL) epitope from the human cytomegalovirus (HCMV) immunodominant matrix protein pp65 efficiently induces systemic CTL responses in HLA‐A*0201 transgenic mice. In this study, we demonstrate that intranasal (i.n.) administration of this lipopeptide, covalently linked to a universal T helper (Th) epitope (PADRE), also induces potent systemic CTL responses. Immune responses were substantially reduced when the unlipidated peptide analogue was used (P<0·01). The induced CTL were CD8+, major histocompatibility complex (MHC) class I‐restricted and CMV specific. Moreover, i.n. administration of this lipidated peptide elicited both systemic and local mucosal CD4+ T‐cell proliferative responses, as well as antigen‐specific delayed type hypersensitivity (DTH) immune responses. In contrast, mice receiving the unlipidated peptide analogue developed substantially reduced Th or DTH responses (P<0·05). These results highlight the usefulness and potential of lipopeptides delivered via mucosal routes as painless, safe, and non‐invasive vaccines.</description><subject>Administration, Intranasal</subject><subject>Animals</subject><subject>Antigens, Viral - immunology</subject><subject>CD4-Positive T-Lymphocytes - immunology</subject><subject>Cell Line</subject><subject>Cytomegalovirus Vaccines - immunology</subject><subject>HLA-A Antigens - immunology</subject><subject>HLA-A2 Antigen</subject><subject>Humans</subject><subject>Hypersensitivity, Delayed - immunology</subject><subject>Immunity, Mucosal</subject><subject>Immunization - methods</subject><subject>Lymphocyte Activation</subject><subject>Malaria Vaccines - immunology</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Original</subject><subject>Phosphoproteins - immunology</subject><subject>T-Lymphocytes, Cytotoxic - immunology</subject><subject>Viral Matrix Proteins - immunology</subject><issn>0019-2805</issn><issn>1365-2567</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkUFv1DAQhS1ERbeFv4AiDtwSPLbj2AeQUAVlpVa9wNlyEqfrKLFD7LTdf4_Drgr0Uk72aL55mjcPoQxwAZjxD30BlJc5KXlVEIxJgYFKXjy8QJvHxku0wRhkTgQuT9FZCH0qKS7LV-gUQFaEU7lBt1sXZ-100EOm29E6G1IdrXeZ7zKdhb2LOxNtkw128pOZom1Ndm_jzi8xTfTLnXYxs65dGhMSHqIZE23HcXEmm02YvAsmvEYnnR6CeXN8z9GPr1--X3zLr24utxefr_KmlIzn0MmuZK2UuK4rzTDULeiasGSy5aZmDQEiO82YBgaCAdVSc1JTwbqaUSLpOfp00J2WejRtY1Z7g5pmO-p5r7y26t-Oszt16-8UVIJwKZLA-6PA7H8uJkQ12tCYYdDO-CWoCjgRQtBnwbQexpKWCXz3BOz9Mrt0BQVS0kqWsKqJA9TMPoTZdI8rA1Zr5qpXa7RqjVatmavfmauHNPr2b8t_Bo8hJ-DjAbi3g9n_t7DaXl-vP_oLYyi9aw</recordid><startdate>200205</startdate><enddate>200205</enddate><creator>BenMohamed, Lbachir</creator><creator>Krishnan, Radhika</creator><creator>Auge, Catherine</creator><creator>Primus, James F.</creator><creator>Diamond, Don J.</creator><general>Blackwell Science Ltd</general><general>Wiley Subscription Services, Inc</general><general>Blackwell Science Inc</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>7QL</scope><scope>7QR</scope><scope>7T5</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>200205</creationdate><title>Intranasal administration of a synthetic lipopeptide without adjuvant induces systemic immune responses</title><author>BenMohamed, Lbachir ; Krishnan, Radhika ; Auge, Catherine ; Primus, James F. ; Diamond, Don J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5946-1f9f54d990bb7a401bd1ab24200d6eb4c2129fa44a1418413a9a62b384fb43293</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Administration, Intranasal</topic><topic>Animals</topic><topic>Antigens, Viral - immunology</topic><topic>CD4-Positive T-Lymphocytes - immunology</topic><topic>Cell Line</topic><topic>Cytomegalovirus Vaccines - immunology</topic><topic>HLA-A Antigens - immunology</topic><topic>HLA-A2 Antigen</topic><topic>Humans</topic><topic>Hypersensitivity, Delayed - immunology</topic><topic>Immunity, Mucosal</topic><topic>Immunization - methods</topic><topic>Lymphocyte Activation</topic><topic>Malaria Vaccines - immunology</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Original</topic><topic>Phosphoproteins - immunology</topic><topic>T-Lymphocytes, Cytotoxic - immunology</topic><topic>Viral Matrix Proteins - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>BenMohamed, Lbachir</creatorcontrib><creatorcontrib>Krishnan, Radhika</creatorcontrib><creatorcontrib>Auge, Catherine</creatorcontrib><creatorcontrib>Primus, James F.</creatorcontrib><creatorcontrib>Diamond, Don J.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>BenMohamed, Lbachir</au><au>Krishnan, Radhika</au><au>Auge, Catherine</au><au>Primus, James F.</au><au>Diamond, Don J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Intranasal administration of a synthetic lipopeptide without adjuvant induces systemic immune responses</atitle><jtitle>Immunology</jtitle><addtitle>Immunology</addtitle><date>2002-05</date><risdate>2002</risdate><volume>106</volume><issue>1</issue><spage>113</spage><epage>121</epage><pages>113-121</pages><issn>0019-2805</issn><eissn>1365-2567</eissn><abstract>Summary
Parenteral injection of a lipopeptide containing a human leucocyte antigen (HLA)‐A*0201‐restricted cytotoxic T‐lymphocyte (CTL) epitope from the human cytomegalovirus (HCMV) immunodominant matrix protein pp65 efficiently induces systemic CTL responses in HLA‐A*0201 transgenic mice. In this study, we demonstrate that intranasal (i.n.) administration of this lipopeptide, covalently linked to a universal T helper (Th) epitope (PADRE), also induces potent systemic CTL responses. Immune responses were substantially reduced when the unlipidated peptide analogue was used (P<0·01). The induced CTL were CD8+, major histocompatibility complex (MHC) class I‐restricted and CMV specific. Moreover, i.n. administration of this lipidated peptide elicited both systemic and local mucosal CD4+ T‐cell proliferative responses, as well as antigen‐specific delayed type hypersensitivity (DTH) immune responses. In contrast, mice receiving the unlipidated peptide analogue developed substantially reduced Th or DTH responses (P<0·05). These results highlight the usefulness and potential of lipopeptides delivered via mucosal routes as painless, safe, and non‐invasive vaccines.</abstract><cop>Oxford, UK</cop><pub>Blackwell Science Ltd</pub><pmid>11972639</pmid><doi>10.1046/j.1365-2567.2002.01396.x</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Administration, Intranasal Animals Antigens, Viral - immunology CD4-Positive T-Lymphocytes - immunology Cell Line Cytomegalovirus Vaccines - immunology HLA-A Antigens - immunology HLA-A2 Antigen Humans Hypersensitivity, Delayed - immunology Immunity, Mucosal Immunization - methods Lymphocyte Activation Malaria Vaccines - immunology Mice Mice, Transgenic Original Phosphoproteins - immunology T-Lymphocytes, Cytotoxic - immunology Viral Matrix Proteins - immunology |
| title | Intranasal administration of a synthetic lipopeptide without adjuvant induces systemic immune responses |
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