Intranasal Immunization with Plasmid DNA-Lipid Complexes Elicits Mucosal Immunity in the Female Genital and Rectal Tracts

The development of vaccines against pathogens transmitted across the genito-rectal mucosa that effectively stimulate both secretory IgA Abs and cytotoxic T lymphocytes in the genital tract and CTL in the draining lymph nodes (LN) has proven a major challenge. Here we report a novel, noninvasive appr...

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Veröffentlicht in:The Journal of immunology (1950) 1999-01, Vol.162 (1), p.254-262
Hauptverfasser: Klavinskis, Linda S, Barnfield, Christina, Gao, Liquan, Parker, Suezanne
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container_title The Journal of immunology (1950)
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creator Klavinskis, Linda S
Barnfield, Christina
Gao, Liquan
Parker, Suezanne
description The development of vaccines against pathogens transmitted across the genito-rectal mucosa that effectively stimulate both secretory IgA Abs and cytotoxic T lymphocytes in the genital tract and CTL in the draining lymph nodes (LN) has proven a major challenge. Here we report a novel, noninvasive approach of genetic vaccination via the intranasal route. Such vaccination elicits immune responses in the genital and rectal mucosa, draining LNs, and central lymphoid system. Intranasal immunization with plasmid DNA-lipid complexes encoding the model Ag firefly luciferase resulted in dissemination of the DNA and the encoded transcript throughout the respiratory and gastrointestinal tracts, draining LNs, and spleen. Complexing the plasmid DNA with the lipid DMRIE/DOPE enhanced expression of the encoded protein in the respiratory tract, increased specific secretory IgA Ab in the vaginal and rectal tracts, and increased the circulating levels of specific IgA and IgG. In addition, intranasal DNA immunization resulted in generation of Ag-specific CTL that were localized in the genital and cervical LNs and spleen. These results suggest that intranasal immunization with plasmid DNA-lipid complexes may represent a generic immunization strategy against pathogens transmitted across the genito-rectal and other mucosal surfaces.
doi_str_mv 10.4049/jimmunol.162.1.254
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These results suggest that intranasal immunization with plasmid DNA-lipid complexes may represent a generic immunization strategy against pathogens transmitted across the genito-rectal and other mucosal surfaces.</description><subject>Administration, Intranasal</subject><subject>Animals</subject><subject>Body Fluids - enzymology</subject><subject>Body Fluids - immunology</subject><subject>Cytotoxicity, Immunologic</subject><subject>Epithelium - enzymology</subject><subject>Epithelium - immunology</subject><subject>Female</subject><subject>Genitalia, Female - immunology</subject><subject>Immunity, Mucosal - immunology</subject><subject>Immunoglobulin A, Secretory - biosynthesis</subject><subject>Immunoglobulin G - biosynthesis</subject><subject>Luciferases - biosynthesis</subject><subject>Luciferases - genetics</subject><subject>Luciferases - immunology</subject><subject>Lymph Nodes - cytology</subject><subject>Lymph Nodes - enzymology</subject><subject>Lymph Nodes - immunology</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Nasal Mucosa - enzymology</subject><subject>Nasal Mucosa - immunology</subject><subject>Phosphatidylethanolamines - administration &amp; dosage</subject><subject>Phosphatidylethanolamines - immunology</subject><subject>Plasmids - immunology</subject><subject>Plasmids - metabolism</subject><subject>Rectum - immunology</subject><subject>RNA, Messenger - metabolism</subject><subject>Spleen - cytology</subject><subject>Spleen - enzymology</subject><subject>Spleen - immunology</subject><subject>T-Lymphocytes, Cytotoxic - enzymology</subject><subject>T-Lymphocytes, Cytotoxic - immunology</subject><subject>Time Factors</subject><subject>Vaccines, DNA - administration &amp; dosage</subject><subject>Vaccines, DNA - immunology</subject><subject>Vagina - enzymology</subject><subject>Vagina - immunology</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkctu2zAQRYmgReo8fiBAAa66k0OKFE0tAzcPA05bBMma4GNcM6AkV6SgOF8fGnHqZVYccO69g5mD0AUlU054ffnsm2ZouzClopzSaVnxIzShVUUKIYj4giaElGVBZ2L2DZ3E-EwIEaTkx-i4llKwmk3QdtGmXrc66oAXuzT_qpPvWjz6tMZ_go6Nd_jnr6ti6Te5mnfNJsALRHwdvPUp4vvBdgd32mLf4rQGfAONDoBvIX_mtm4dfgC7Kx97bVM8Q19XOkQ437-n6Onm-nF-Vyx_3y7mV8vC5h1TYamsLDfCAuiSGVOtahBGSmdWxsm8ETPUCsmEg5JJ5pg0Tkg6k85yIWtgp-jHe-6m7_4NEJNqfLQQgm6hG6ISdcXzOepPhXRGOa_pTli-C23fxdjDSm163-h-qyhROzDqA4zKYBRVGUw2fd-nD6YB99-yJ3GYvvZ_16PvQcV8v5DVVI3jeAh6A18SmqI</recordid><startdate>19990101</startdate><enddate>19990101</enddate><creator>Klavinskis, Linda S</creator><creator>Barnfield, Christina</creator><creator>Gao, Liquan</creator><creator>Parker, Suezanne</creator><general>Am Assoc Immnol</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>7QO</scope><scope>7T5</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>19990101</creationdate><title>Intranasal Immunization with Plasmid DNA-Lipid Complexes Elicits Mucosal Immunity in the Female Genital and Rectal Tracts</title><author>Klavinskis, Linda S ; 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subjects Administration, Intranasal
Animals
Body Fluids - enzymology
Body Fluids - immunology
Cytotoxicity, Immunologic
Epithelium - enzymology
Epithelium - immunology
Female
Genitalia, Female - immunology
Immunity, Mucosal - immunology
Immunoglobulin A, Secretory - biosynthesis
Immunoglobulin G - biosynthesis
Luciferases - biosynthesis
Luciferases - genetics
Luciferases - immunology
Lymph Nodes - cytology
Lymph Nodes - enzymology
Lymph Nodes - immunology
Mice
Mice, Inbred BALB C
Nasal Mucosa - enzymology
Nasal Mucosa - immunology
Phosphatidylethanolamines - administration & dosage
Phosphatidylethanolamines - immunology
Plasmids - immunology
Plasmids - metabolism
Rectum - immunology
RNA, Messenger - metabolism
Spleen - cytology
Spleen - enzymology
Spleen - immunology
T-Lymphocytes, Cytotoxic - enzymology
T-Lymphocytes, Cytotoxic - immunology
Time Factors
Vaccines, DNA - administration & dosage
Vaccines, DNA - immunology
Vagina - enzymology
Vagina - immunology
title Intranasal Immunization with Plasmid DNA-Lipid Complexes Elicits Mucosal Immunity in the Female Genital and Rectal Tracts
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