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Sublingual vaccination induces mucosal and systemic adaptive immunity for protection against lung tumor challenge
Sublingual route offers a safer and more practical approach for delivering vaccines relative to other systemic and mucosal immunization strategies. Here we present evidence demonstrating protection against ovalbumin expressing B16 (B16-OVA) metastatic melanoma lung tumor formation by sublingual vacc...
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| Published in: | PloS one 2014-03, Vol.9 (3), p.e90001-e90001 |
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| creator | Singh, Shailbala Yang, Guojun Schluns, Kimberly S Anthony, Scott M Sastry, K Jagannadha |
| description | Sublingual route offers a safer and more practical approach for delivering vaccines relative to other systemic and mucosal immunization strategies. Here we present evidence demonstrating protection against ovalbumin expressing B16 (B16-OVA) metastatic melanoma lung tumor formation by sublingual vaccination with the model tumor antigen OVA plus synthetic glycolipid alpha-galactosylceramide (aGalCer) for harnessing the adjuvant potential of natural killer T (NKT) cells, which effectively bridge innate and adaptive arms of the immune system. The protective efficacy of immunization with OVA plus aGalCer was antigen-specific as immunized mice challenged with parental B16 tumors lacking OVA expression were not protected. Multiple sublingual immunizations in the presence, but not in the absence of aGalCer, resulted in repeated activation of NKT cells in the draining lymph nodes, spleens, and lungs of immunized animals concurrent with progressively increasing OVA-specific CD8+ T cell responses as well as serum IgG and vaginal IgA levels. Furthermore, sublingual administration of the antigen only in the presence of the aGalCer adjuvant effectively boosted the OVA-specific immune responses. These results support potential clinical utility of sublingual route of vaccination with aGalCer-for prevention of pulmonary metastases. |
| doi_str_mv | 10.1371/journal.pone.0090001 |
| format | article |
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Here we present evidence demonstrating protection against ovalbumin expressing B16 (B16-OVA) metastatic melanoma lung tumor formation by sublingual vaccination with the model tumor antigen OVA plus synthetic glycolipid alpha-galactosylceramide (aGalCer) for harnessing the adjuvant potential of natural killer T (NKT) cells, which effectively bridge innate and adaptive arms of the immune system. The protective efficacy of immunization with OVA plus aGalCer was antigen-specific as immunized mice challenged with parental B16 tumors lacking OVA expression were not protected. Multiple sublingual immunizations in the presence, but not in the absence of aGalCer, resulted in repeated activation of NKT cells in the draining lymph nodes, spleens, and lungs of immunized animals concurrent with progressively increasing OVA-specific CD8+ T cell responses as well as serum IgG and vaginal IgA levels. 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These results support potential clinical utility of sublingual route of vaccination with aGalCer-for prevention of pulmonary metastases.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0090001</identifier><identifier>PMID: 24599269</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adaptive Immunity ; Adjuvants, Immunologic - administration & dosage ; Administration, Sublingual ; Albumin ; Analysis ; Animals ; Antigens ; Antigens, Neoplasm - immunology ; Biology ; Cancer metastasis ; Cancer prevention ; Cancer therapies ; Cancer vaccines ; Cancer Vaccines - administration & dosage ; Cell Line, Tumor ; Cytotoxicity ; Dendritic cells ; Dendritic Cells - immunology ; Female ; Galactosylceramides - administration & dosage ; Immune response ; Immune system ; Immunity, Humoral ; Immunization ; Immunoglobulin A ; Immunology ; Influenza ; Laboratory animals ; Lung cancer ; Lung Neoplasms - immunology ; Lung Neoplasms - prevention & control ; Lung Neoplasms - secondary ; Lymph nodes ; Lymphocytes ; Lymphocytes T ; Melanoma ; Melanoma, Experimental - immunology ; Melanoma, Experimental - prevention & control ; Melanoma, Experimental - secondary ; Metastasis ; Mice, Inbred C57BL ; Mouth Mucosa - immunology ; Natural Killer T-Cells - immunology ; Neoplasm Transplantation ; Ovalbumin - immunology ; Parenting ; Penicillin ; Studies ; T cell receptors ; T cells ; Tumors ; Vaccination ; Vaccines ; Viral infections ; Viruses</subject><ispartof>PloS one, 2014-03, Vol.9 (3), p.e90001-e90001</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Singh et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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Here we present evidence demonstrating protection against ovalbumin expressing B16 (B16-OVA) metastatic melanoma lung tumor formation by sublingual vaccination with the model tumor antigen OVA plus synthetic glycolipid alpha-galactosylceramide (aGalCer) for harnessing the adjuvant potential of natural killer T (NKT) cells, which effectively bridge innate and adaptive arms of the immune system. The protective efficacy of immunization with OVA plus aGalCer was antigen-specific as immunized mice challenged with parental B16 tumors lacking OVA expression were not protected. Multiple sublingual immunizations in the presence, but not in the absence of aGalCer, resulted in repeated activation of NKT cells in the draining lymph nodes, spleens, and lungs of immunized animals concurrent with progressively increasing OVA-specific CD8+ T cell responses as well as serum IgG and vaginal IgA levels. 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Singh, Shailbala</au><au>Yang, Guojun</au><au>Schluns, Kimberly S</au><au>Anthony, Scott M</au><au>Sastry, K Jagannadha</au><au>Rodrigues, Mauricio Martins</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sublingual vaccination induces mucosal and systemic adaptive immunity for protection against lung tumor challenge</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-03-05</date><risdate>2014</risdate><volume>9</volume><issue>3</issue><spage>e90001</spage><epage>e90001</epage><pages>e90001-e90001</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Sublingual route offers a safer and more practical approach for delivering vaccines relative to other systemic and mucosal immunization strategies. Here we present evidence demonstrating protection against ovalbumin expressing B16 (B16-OVA) metastatic melanoma lung tumor formation by sublingual vaccination with the model tumor antigen OVA plus synthetic glycolipid alpha-galactosylceramide (aGalCer) for harnessing the adjuvant potential of natural killer T (NKT) cells, which effectively bridge innate and adaptive arms of the immune system. The protective efficacy of immunization with OVA plus aGalCer was antigen-specific as immunized mice challenged with parental B16 tumors lacking OVA expression were not protected. Multiple sublingual immunizations in the presence, but not in the absence of aGalCer, resulted in repeated activation of NKT cells in the draining lymph nodes, spleens, and lungs of immunized animals concurrent with progressively increasing OVA-specific CD8+ T cell responses as well as serum IgG and vaginal IgA levels. Furthermore, sublingual administration of the antigen only in the presence of the aGalCer adjuvant effectively boosted the OVA-specific immune responses. These results support potential clinical utility of sublingual route of vaccination with aGalCer-for prevention of pulmonary metastases.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24599269</pmid><doi>10.1371/journal.pone.0090001</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Adaptive Immunity Adjuvants, Immunologic - administration & dosage Administration, Sublingual Albumin Analysis Animals Antigens Antigens, Neoplasm - immunology Biology Cancer metastasis Cancer prevention Cancer therapies Cancer vaccines Cancer Vaccines - administration & dosage Cell Line, Tumor Cytotoxicity Dendritic cells Dendritic Cells - immunology Female Galactosylceramides - administration & dosage Immune response Immune system Immunity, Humoral Immunization Immunoglobulin A Immunology Influenza Laboratory animals Lung cancer Lung Neoplasms - immunology Lung Neoplasms - prevention & control Lung Neoplasms - secondary Lymph nodes Lymphocytes Lymphocytes T Melanoma Melanoma, Experimental - immunology Melanoma, Experimental - prevention & control Melanoma, Experimental - secondary Metastasis Mice, Inbred C57BL Mouth Mucosa - immunology Natural Killer T-Cells - immunology Neoplasm Transplantation Ovalbumin - immunology Parenting Penicillin Studies T cell receptors T cells Tumors Vaccination Vaccines Viral infections Viruses |
| title | Sublingual vaccination induces mucosal and systemic adaptive immunity for protection against lung tumor challenge |
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