Effective vaginal DNA delivery with high transfection efficiency is a good system for induction of higher local vaginal immune responses
Identifieur interne : 002E16 ( Main/Exploration ); précédent : 002E15; suivant : 002E17Effective vaginal DNA delivery with high transfection efficiency is a good system for induction of higher local vaginal immune responses
Auteurs : Takanori Kanazawa [Japon] ; Yuuki Takashima [Japon] ; Yasunori Shibata [Japon] ; Miki Tsuchiya [Japon] ; Toshiaki Tamura [Japon] ; Hiroaki Okada [Japon]Source :
- Journal of Pharmacy and Pharmacology [ 0022-3573 ] ; 2009-11.
Abstract
Objectives To investigate the local vaginal and systemic immune responses of effective vaginal DNA delivery with high transfection efficiency, we determined the effects on Th1‐dependent cytokine (interferon‐γ) production in spleen and inguinal lymph node cells and antibody responses of vaginal pDNA immunization with a cell‐penetrating peptide, and compared our vaginal immunization with intradermal and intranasal immunizations. Methods Mice were immunized by vaginal, nasal or dermal administration of pCMV‐OVA with or without peptide carriers, and serum, vaginal fluids, spleen and inguinal cells were harvested. The serum immunoglobulin (Ig)G2a and vaginal IgA antibody responses were determined by sandwich enzyme‐linked immunosorbent assay (ELISA). The interferon‐γ production from spleen cells or inguinal lymph node cells was determined by an ELISA kit. Key findings The direct vaginal immunization strongly induced IgA in the vaginal fluids and interferon‐γ production in the local lymph node draining from the vagina. In addition, co‐vaccination with the peptide carriers elevated these immune responses compared with vaccination with pCMV‐OVA alone. Vaginal immunization with high transfection efficiency promoted vaginal IgA production to a significantly greater extent than intradermal or nasal immunization. Conclusions These results suggested that direct vaginal DNA vaccines under high transfection conditions induced higher local vaginal antibody than that by intranasal or intradermal administration, and peptide carriers effectively elevated mucosal immune responses. Therefore, this vaginal DNA vaccination method may be expected to be useful in the prevention and treatment methods for vaginal infectious diseases such as HIV infection.
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DOI: 10.1211/jpp.61.11.0004
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type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Tsuchiya, Miki" sort="Tsuchiya, Miki" uniqKey="Tsuchiya M" first="Miki" last="Tsuchiya">Miki Tsuchiya</name><affiliation wicri:level="3"><country xml:lang="fr">Japon</country><wicri:regionArea>Laboratory of Pharmaceutics and Drug Delivery, Department of Pharmaceutical Science, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Tamura, Toshiaki" sort="Tamura, Toshiaki" uniqKey="Tamura T" first="Toshiaki" last="Tamura">Toshiaki Tamura</name><affiliation wicri:level="3"><country xml:lang="fr">Japon</country><wicri:regionArea>Laboratory of Pharmaceutics and Drug Delivery, Department of Pharmaceutical Science, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, 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unit="issue">11</biblScope><biblScope unit="page" from="1457">1457</biblScope><biblScope unit="page" to="1463">1463</biblScope><biblScope unit="page-count">7</biblScope><publisher>Blackwell Publishing Ltd</publisher><pubPlace>Oxford, UK</pubPlace><date type="published" when="2009-11">2009-11</date></imprint><idno type="ISSN">0022-3573</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0022-3573</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Objectives To investigate the local vaginal and systemic immune responses of effective vaginal DNA delivery with high transfection efficiency, we determined the effects on Th1‐dependent cytokine (interferon‐γ) production in spleen and inguinal lymph node cells and antibody responses of vaginal pDNA immunization with a cell‐penetrating peptide, and compared our vaginal immunization with intradermal and intranasal immunizations. Methods Mice were immunized by vaginal, nasal or dermal administration of pCMV‐OVA with or without peptide carriers, and serum, vaginal fluids, spleen and inguinal cells were harvested. The serum immunoglobulin (Ig)G2a and vaginal IgA antibody responses were determined by sandwich enzyme‐linked immunosorbent assay (ELISA). The interferon‐γ production from spleen cells or inguinal lymph node cells was determined by an ELISA kit. Key findings The direct vaginal immunization strongly induced IgA in the vaginal fluids and interferon‐γ production in the local lymph node draining from the vagina. In addition, co‐vaccination with the peptide carriers elevated these immune responses compared with vaccination with pCMV‐OVA alone. Vaginal immunization with high transfection efficiency promoted vaginal IgA production to a significantly greater extent than intradermal or nasal immunization. Conclusions These results suggested that direct vaginal DNA vaccines under high transfection conditions induced higher local vaginal antibody than that by intranasal or intradermal administration, and peptide carriers effectively elevated mucosal immune responses. Therefore, this vaginal DNA vaccination method may be expected to be useful in the prevention and treatment methods for vaginal infectious diseases such as HIV infection.</div></front></TEI><affiliations><list><country><li>Japon</li></country><region><li>Région de Kantō</li></region><settlement><li>Tokyo</li></settlement></list><tree><country name="Japon"><region name="Région de Kantō"><name sortKey="Kanazawa, Takanori" sort="Kanazawa, Takanori" uniqKey="Kanazawa T" first="Takanori" last="Kanazawa">Takanori Kanazawa</name></region><name sortKey="Kanazawa, Takanori" sort="Kanazawa, Takanori" uniqKey="Kanazawa T" first="Takanori" last="Kanazawa">Takanori Kanazawa</name><name sortKey="Okada, Hiroaki" sort="Okada, Hiroaki" uniqKey="Okada H" first="Hiroaki" last="Okada">Hiroaki Okada</name><name sortKey="Shibata, Yasunori" sort="Shibata, Yasunori" uniqKey="Shibata Y" first="Yasunori" last="Shibata">Yasunori Shibata</name><name sortKey="Takashima, Yuuki" sort="Takashima, Yuuki" uniqKey="Takashima Y" first="Yuuki" last="Takashima">Yuuki Takashima</name><name sortKey="Tamura, Toshiaki" sort="Tamura, Toshiaki" uniqKey="Tamura T" first="Toshiaki" last="Tamura">Toshiaki Tamura</name><name sortKey="Tsuchiya, Miki" sort="Tsuchiya, Miki" uniqKey="Tsuchiya M" first="Miki" last="Tsuchiya">Miki Tsuchiya</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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