{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T21:34:41Z","timestamp":1791840881180,"version":"4.3.4"},"reference-count":60,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2009,12,1]],"date-time":"2009-12-01T00:00:00Z","timestamp":1259625600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>We have recently reported that the sublingual (s.l.) mucosa is an efficient site for inducing systemic and mucosal immune responses. In this study, the potential of s.l. immunization to induce remote Ab responses and CD8+ cytotoxic responses in the female genital tract was examined in mice by using a nonreplicating Ag, OVA, and cholera toxin (CT) as an adjuvant. Sublingual administration of OVA and CT induced Ag-specific IgA and IgG Abs in blood and in cervicovaginal secretions. These responses were associated with large numbers of IgA Ab-secreting cells (ASCs) in the genital mucosa. Genital ASC responses were similar in magnitude and isotype distribution after s.l., intranasal, or vaginal immunization and were superior to those seen after intragastric immunization. Genital, but not blood or spleen, IgA ASC responses were inhibited by treatment with anti-CCL28 Abs, suggesting that the chemokine CCL28 plays a major role in the migration of IgA ASC progenitors to the reproductive tract mucosa. Furthermore, s.l. immunization with OVA induced OVA-specific effector CD8+ cytolytic T cells in the genital mucosa, and these responses required coadministration of the CT adjuvant. Furthermore, s.l. administration of human papillomavirus virus-like particles with or without the CT adjuvant conferred protection against genital challenge with human papillomavirus pseudovirions. Taken together, these findings underscore the potential of s.l. immunization as an efficient vaccination strategy for inducing genital immune responses and should impact on the development of vaccines against sexually transmitted diseases.<\/jats:p>","DOI":"10.4049\/jimmunol.0803740","type":"journal-article","created":{"date-parts":[[2009,11,23]],"date-time":"2009-11-23T22:59:20Z","timestamp":1259017160000},"page":"7851-7859","source":"Crossref","is-referenced-by-count":94,"title":["Sublingual Immunization with Nonreplicating Antigens Induces Antibody-Forming Cells and Cytotoxic T Cells in the Female Genital Tract Mucosa and Protects against Genital Papillomavirus Infection"],"prefix":"10.1093","volume":"183","author":[{"given":"Nicolas","family":"\u00c7uburu","sequence":"first","affiliation":[{"name":"Laboratory Sciences Division, International Vaccine Institute , Seoul,","place":["Korea"]},{"name":"INSERM, Unit\u00e9 Mixte de Recherche 721, Facult\u00e9 de M\u00e9decine Pasteur, Universit\u00e9 de Nice-Sophia-Antipolis , Nice,","place":["France"]},{"name":"Laboratory of Cellular Oncology, National Cancer Institute, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi-Na","family":"Kweon","sequence":"additional","affiliation":[{"name":"Laboratory Sciences Division, International Vaccine Institute , Seoul,","place":["Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Hervouet","sequence":"additional","affiliation":[{"name":"INSERM, Unit\u00e9 Mixte de Recherche 721, Facult\u00e9 de M\u00e9decine Pasteur, Universit\u00e9 de Nice-Sophia-Antipolis , Nice,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye-Ran","family":"Cha","sequence":"additional","affiliation":[{"name":"Laboratory Sciences Division, International Vaccine Institute , Seoul,","place":["Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuk-Ying S","family":"Pang","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Oncology, National Cancer Institute, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Holmgren","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology and G\u00f6teborg University Vaccine Research Institute , G\u00f6teborg,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konrad","family":"Stadler","sequence":"additional","affiliation":[{"name":"Laboratory Sciences Division, International Vaccine Institute , Seoul,","place":["Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John T","family":"Schiller","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Oncology, National Cancer Institute, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabienne","family":"Anju\u00e8re","sequence":"additional","affiliation":[{"name":"INSERM, Unit\u00e9 Mixte de Recherche 721, Facult\u00e9 de M\u00e9decine Pasteur, Universit\u00e9 de Nice-Sophia-Antipolis , Nice,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecil","family":"Czerkinsky","sequence":"additional","affiliation":[{"name":"Laboratory Sciences Division, International Vaccine Institute , Seoul,","place":["Korea"]},{"name":"INSERM, Unit\u00e9 Mixte de Recherche 721, Facult\u00e9 de M\u00e9decine Pasteur, Universit\u00e9 de Nice-Sophia-Antipolis , Nice,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,12,15]]},"reference":[{"key":"2026012811224380800_R1","first-page":"388","article-title":"Human papillomavirus vaccines versus cervical cancer screening.","volume-title":"Clin. 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Immunol.","year":"2003"},{"key":"2026012811224380800_R7","first-page":"265","article-title":"The common mucosal immune system and current strategies for induction of immune responses in external secretions.","volume-title":"J. Clin. Immunol.","year":"1987"},{"key":"2026012811224380800_R8","first-page":"1709","article-title":"Mucosal immunization with HIV-1 peptide vaccine induces mucosal and systemic cytotoxic T lymphocytes and protective immunity in mice against intrarectal recombinant HIV-vaccinia challenge.","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1998"},{"key":"2026012811224380800_R9","first-page":"1879","article-title":"Long-lived cytotoxic T lymphocyte memory in mucosal tissues after mucosal but not systemic immunization.","volume-title":"J. Exp. 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