Methylglycol chitosan and a synthetic TLR4 agonist enhance immune responses to influenza vaccine administered sublingually
Abstract Influenza is a vaccine-preventable contagious respiratory illness caused by influenza (flu) viruses which can lead to hospitalization and sometimes even death. Current flu vaccines delivered intramuscularly (IM) or intradermally (ID) are less effective at eliciting protective mucosal immune...
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| Veröffentlicht in: | Vaccine 2015-10, Vol.33 (43), p.5845-5853 |
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| creator | Spinner, Justin L Oberoi, Hardeep S Yorgensen, Yvonne M Poirier, Danielle S Burkhart, David J Plante, Martin Evans, Jay T |
| description | Abstract Influenza is a vaccine-preventable contagious respiratory illness caused by influenza (flu) viruses which can lead to hospitalization and sometimes even death. Current flu vaccines delivered intramuscularly (IM) or intradermally (ID) are less effective at eliciting protective mucosal immune responses and vaccines delivered intranasally (IN) possess potential safety concerns. Sublingual (SL) vaccination is a promising alternative route for vaccine delivery which has been indicated as safe and effective at inducing protective immune responses in both systemic and mucosal compartments. We evaluated the efficacy of methylglycol chitosan (MGC) and a synthetic toll-like receptor 4 agonist (CRX-601), alone or in combination, for improving systemic and mucosal immune responses to a monovalent detergent-split flu virus vaccine delivered SL. SL vaccination of mice with split-flu vaccine formulated with either MGC or CRX-601 resulted in specific serum IgG and mucosal IgA titers that were significantly greater than titers from non-adjuvanted vaccination and equivalent to or greater than titers in mice vaccinated IM. Our results demonstrate that SL vaccination utilizing MGC or CRX-601 as adjuvants is a viable alternative route of vaccination for flu which can elicit systemic immune responses equivalent to or greater than IM vaccination with the added benefit of stimulating a robust specific mucosal immune response. |
| doi_str_mv | 10.1016/j.vaccine.2015.08.086 |
| format | Article |
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Current flu vaccines delivered intramuscularly (IM) or intradermally (ID) are less effective at eliciting protective mucosal immune responses and vaccines delivered intranasally (IN) possess potential safety concerns. Sublingual (SL) vaccination is a promising alternative route for vaccine delivery which has been indicated as safe and effective at inducing protective immune responses in both systemic and mucosal compartments. We evaluated the efficacy of methylglycol chitosan (MGC) and a synthetic toll-like receptor 4 agonist (CRX-601), alone or in combination, for improving systemic and mucosal immune responses to a monovalent detergent-split flu virus vaccine delivered SL. SL vaccination of mice with split-flu vaccine formulated with either MGC or CRX-601 resulted in specific serum IgG and mucosal IgA titers that were significantly greater than titers from non-adjuvanted vaccination and equivalent to or greater than titers in mice vaccinated IM. Our results demonstrate that SL vaccination utilizing MGC or CRX-601 as adjuvants is a viable alternative route of vaccination for flu which can elicit systemic immune responses equivalent to or greater than IM vaccination with the added benefit of stimulating a robust specific mucosal immune response.</description><identifier>ISSN: 0264-410X</identifier><identifier>EISSN: 1873-2518</identifier><identifier>DOI: 10.1016/j.vaccine.2015.08.086</identifier><identifier>PMID: 26392012</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>Adjuvants, Immunologic - administration & dosage ; Administration, Sublingual ; Allergy and Immunology ; Animals ; Antibodies, Viral - blood ; Antibodies, Viral - immunology ; Chitosan ; Chitosan - administration & dosage ; CRX-601 ; Female ; Immune response ; Immunity, Mucosal ; Immunoglobulin A - analysis ; Immunoglobulin G - blood ; Infections ; Influenza ; Influenza Vaccines - administration & dosage ; Influenza Vaccines - immunology ; Mice, Inbred BALB C ; Mucosal vaccination ; Particle size ; Sublingual ; TLR-4 ; Toll-Like Receptor 4 - agonists ; Treatment Outcome ; Vaccines ; Vaccines, Inactivated - administration & dosage ; Vaccines, Inactivated - immunology</subject><ispartof>Vaccine, 2015-10, Vol.33 (43), p.5845-5853</ispartof><rights>Elsevier Ltd</rights><rights>2015 Elsevier Ltd</rights><rights>Copyright © 2015 Elsevier Ltd. All rights reserved.</rights><rights>Copyright Elsevier Limited Oct 26, 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c616t-4e5a906c795f2002a754367a8fa799fb008047d85dd3a70c733ba325ff9e7ac13</citedby><cites>FETCH-LOGICAL-c616t-4e5a906c795f2002a754367a8fa799fb008047d85dd3a70c733ba325ff9e7ac13</cites><orcidid>0000-0001-6602-0272 ; 0000-0002-8139-5539</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/1722465909?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>230,315,782,786,887,3554,27933,27934,46004,64394,64396,64398,72478</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26392012$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Spinner, Justin L</creatorcontrib><creatorcontrib>Oberoi, Hardeep S</creatorcontrib><creatorcontrib>Yorgensen, Yvonne M</creatorcontrib><creatorcontrib>Poirier, Danielle S</creatorcontrib><creatorcontrib>Burkhart, David J</creatorcontrib><creatorcontrib>Plante, Martin</creatorcontrib><creatorcontrib>Evans, Jay T</creatorcontrib><title>Methylglycol chitosan and a synthetic TLR4 agonist enhance immune responses to influenza vaccine administered sublingually</title><title>Vaccine</title><addtitle>Vaccine</addtitle><description>Abstract Influenza is a vaccine-preventable contagious respiratory illness caused by influenza (flu) viruses which can lead to hospitalization and sometimes even death. Current flu vaccines delivered intramuscularly (IM) or intradermally (ID) are less effective at eliciting protective mucosal immune responses and vaccines delivered intranasally (IN) possess potential safety concerns. Sublingual (SL) vaccination is a promising alternative route for vaccine delivery which has been indicated as safe and effective at inducing protective immune responses in both systemic and mucosal compartments. We evaluated the efficacy of methylglycol chitosan (MGC) and a synthetic toll-like receptor 4 agonist (CRX-601), alone or in combination, for improving systemic and mucosal immune responses to a monovalent detergent-split flu virus vaccine delivered SL. SL vaccination of mice with split-flu vaccine formulated with either MGC or CRX-601 resulted in specific serum IgG and mucosal IgA titers that were significantly greater than titers from non-adjuvanted vaccination and equivalent to or greater than titers in mice vaccinated IM. Our results demonstrate that SL vaccination utilizing MGC or CRX-601 as adjuvants is a viable alternative route of vaccination for flu which can elicit systemic immune responses equivalent to or greater than IM vaccination with the added benefit of stimulating a robust specific mucosal immune response.</description><subject>Adjuvants, Immunologic - administration & dosage</subject><subject>Administration, Sublingual</subject><subject>Allergy and Immunology</subject><subject>Animals</subject><subject>Antibodies, Viral - blood</subject><subject>Antibodies, Viral - immunology</subject><subject>Chitosan</subject><subject>Chitosan - administration & dosage</subject><subject>CRX-601</subject><subject>Female</subject><subject>Immune response</subject><subject>Immunity, Mucosal</subject><subject>Immunoglobulin A - analysis</subject><subject>Immunoglobulin G - blood</subject><subject>Infections</subject><subject>Influenza</subject><subject>Influenza Vaccines - administration & dosage</subject><subject>Influenza Vaccines - immunology</subject><subject>Mice, Inbred BALB C</subject><subject>Mucosal vaccination</subject><subject>Particle size</subject><subject>Sublingual</subject><subject>TLR-4</subject><subject>Toll-Like Receptor 4 - agonists</subject><subject>Treatment Outcome</subject><subject>Vaccines</subject><subject>Vaccines, Inactivated - administration & dosage</subject><subject>Vaccines, Inactivated - immunology</subject><issn>0264-410X</issn><issn>1873-2518</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFUk2P0zAQjRCIXRZ-AsgSFy4tYztx4ssitOJLKkKCReJmuc6kdXHsYieVsr8eh5YF9oI0kg9-7828eVMUTyksKVDxcrc8aGOsxyUDWi2hySXuFee0qfmCVbS5X5wDE-WipPDtrHiU0g4AKk7lw-KMCS4zjZ0XNx9x2E5u4yYTHDFbO4SkPdG-JZqkyQ9bHKwh16vPJdGb4G0aCPqt9gaJ7fvRI4mY9sEnTGQIxPrOjehvNDmNR3Tb25mGEVuSxrWzfjNq56bHxYNOu4RPTu9F8fXtm-ur94vVp3cfrl6vFkZQMSxKrLQEYWpZdQyA6boquah10-laym4N0EBZt03VtlzXYGrO15qzqusk1tpQflFcHnX347rH1qAfonZqH22v46SCturfH2-3ahMOqhQgBeNZ4MVJIIYfI6ZB9TYZdE57DGNStGZMciipzNDnd6C7MEaf7f1ClaKSMKOqI8rEkFLE7nYYCmpOV-3UaX1qTldBk0tk3rO_ndyyfseZAa-OAMz7PFiMKhmLOavWRjSDaoP9b4vLOwomB2aNdt9xwvTHjUpMgfoyn9h8YbSa-0vBfwKrutCH</recordid><startdate>20151026</startdate><enddate>20151026</enddate><creator>Spinner, Justin L</creator><creator>Oberoi, Hardeep S</creator><creator>Yorgensen, Yvonne M</creator><creator>Poirier, Danielle S</creator><creator>Burkhart, David J</creator><creator>Plante, Martin</creator><creator>Evans, Jay T</creator><general>Elsevier Ltd</general><general>Elsevier Limited</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>3V.</scope><scope>7QL</scope><scope>7RV</scope><scope>7T2</scope><scope>7T5</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88C</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0R</scope><scope>M0S</scope><scope>M0T</scope><scope>M1P</scope><scope>M2O</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-6602-0272</orcidid><orcidid>https://orcid.org/0000-0002-8139-5539</orcidid></search><sort><creationdate>20151026</creationdate><title>Methylglycol chitosan and a synthetic TLR4 agonist enhance immune responses to influenza vaccine administered sublingually</title><author>Spinner, Justin L ; Oberoi, Hardeep S ; Yorgensen, Yvonne M ; Poirier, Danielle S ; Burkhart, David J ; Plante, Martin ; Evans, Jay T</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c616t-4e5a906c795f2002a754367a8fa799fb008047d85dd3a70c733ba325ff9e7ac13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adjuvants, Immunologic - administration & dosage</topic><topic>Administration, Sublingual</topic><topic>Allergy and Immunology</topic><topic>Animals</topic><topic>Antibodies, Viral - blood</topic><topic>Antibodies, Viral - immunology</topic><topic>Chitosan</topic><topic>Chitosan - administration & dosage</topic><topic>CRX-601</topic><topic>Female</topic><topic>Immune response</topic><topic>Immunity, Mucosal</topic><topic>Immunoglobulin A - analysis</topic><topic>Immunoglobulin G - blood</topic><topic>Infections</topic><topic>Influenza</topic><topic>Influenza Vaccines - administration & dosage</topic><topic>Influenza Vaccines - immunology</topic><topic>Mice, Inbred BALB C</topic><topic>Mucosal vaccination</topic><topic>Particle size</topic><topic>Sublingual</topic><topic>TLR-4</topic><topic>Toll-Like Receptor 4 - agonists</topic><topic>Treatment Outcome</topic><topic>Vaccines</topic><topic>Vaccines, Inactivated - administration & dosage</topic><topic>Vaccines, Inactivated - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Spinner, Justin L</creatorcontrib><creatorcontrib>Oberoi, Hardeep S</creatorcontrib><creatorcontrib>Yorgensen, Yvonne M</creatorcontrib><creatorcontrib>Poirier, Danielle S</creatorcontrib><creatorcontrib>Burkhart, David J</creatorcontrib><creatorcontrib>Plante, Martin</creatorcontrib><creatorcontrib>Evans, Jay T</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Nursing & Allied Health Database</collection><collection>Health and Safety Science Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Healthcare Administration Database (Alumni)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Healthcare Administration Database</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Vaccine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Spinner, Justin L</au><au>Oberoi, Hardeep S</au><au>Yorgensen, Yvonne M</au><au>Poirier, Danielle S</au><au>Burkhart, David J</au><au>Plante, Martin</au><au>Evans, Jay T</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Methylglycol chitosan and a synthetic TLR4 agonist enhance immune responses to influenza vaccine administered sublingually</atitle><jtitle>Vaccine</jtitle><addtitle>Vaccine</addtitle><date>2015-10-26</date><risdate>2015</risdate><volume>33</volume><issue>43</issue><spage>5845</spage><epage>5853</epage><pages>5845-5853</pages><issn>0264-410X</issn><eissn>1873-2518</eissn><abstract>Abstract Influenza is a vaccine-preventable contagious respiratory illness caused by influenza (flu) viruses which can lead to hospitalization and sometimes even death. Current flu vaccines delivered intramuscularly (IM) or intradermally (ID) are less effective at eliciting protective mucosal immune responses and vaccines delivered intranasally (IN) possess potential safety concerns. Sublingual (SL) vaccination is a promising alternative route for vaccine delivery which has been indicated as safe and effective at inducing protective immune responses in both systemic and mucosal compartments. We evaluated the efficacy of methylglycol chitosan (MGC) and a synthetic toll-like receptor 4 agonist (CRX-601), alone or in combination, for improving systemic and mucosal immune responses to a monovalent detergent-split flu virus vaccine delivered SL. SL vaccination of mice with split-flu vaccine formulated with either MGC or CRX-601 resulted in specific serum IgG and mucosal IgA titers that were significantly greater than titers from non-adjuvanted vaccination and equivalent to or greater than titers in mice vaccinated IM. Our results demonstrate that SL vaccination utilizing MGC or CRX-601 as adjuvants is a viable alternative route of vaccination for flu which can elicit systemic immune responses equivalent to or greater than IM vaccination with the added benefit of stimulating a robust specific mucosal immune response.</abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>26392012</pmid><doi>10.1016/j.vaccine.2015.08.086</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0001-6602-0272</orcidid><orcidid>https://orcid.org/0000-0002-8139-5539</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adjuvants, Immunologic - administration & dosage Administration, Sublingual Allergy and Immunology Animals Antibodies, Viral - blood Antibodies, Viral - immunology Chitosan Chitosan - administration & dosage CRX-601 Female Immune response Immunity, Mucosal Immunoglobulin A - analysis Immunoglobulin G - blood Infections Influenza Influenza Vaccines - administration & dosage Influenza Vaccines - immunology Mice, Inbred BALB C Mucosal vaccination Particle size Sublingual TLR-4 Toll-Like Receptor 4 - agonists Treatment Outcome Vaccines Vaccines, Inactivated - administration & dosage Vaccines, Inactivated - immunology |
| title | Methylglycol chitosan and a synthetic TLR4 agonist enhance immune responses to influenza vaccine administered sublingually |
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