Effect of adjuvants on responses to skin immunization by microneedles coated with influenza subunit vaccine
Recent studies have demonstrated the effectiveness of vaccine delivery to the skin by vaccine-coated microneedles; however there is little information on the effects of adjuvants using this approach for vaccination. Here we investigate the use of TLR ligands as adjuvants with skin-based delivery of...
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| creator | Weldon, William C Zarnitsyn, Vladimir G Esser, E Stein Taherbhai, Misha T Koutsonanos, Dimitrios G Vassilieva, Elena V Skountzou, Ioanna Prausnitz, Mark R Compans, Richard W |
| description | Recent studies have demonstrated the effectiveness of vaccine delivery to the skin by vaccine-coated microneedles; however there is little information on the effects of adjuvants using this approach for vaccination. Here we investigate the use of TLR ligands as adjuvants with skin-based delivery of influenza subunit vaccine. BALB/c mice received 1 µg of monovalent H1N1 subunit vaccine alone or with 1 µg of imiquimod or poly(I:C) individually or in combination via coated microneedle patches inserted into the skin. Poly(I:C) adjuvanted subunit influenza vaccine induced similar antigen-specific immune responses compared to vaccine alone when delivered to the skin by microneedles. However, imiquimod-adjuvanted vaccine elicited higher levels of serum IgG2a antibodies and increased hemagglutination inhibition titers compared to vaccine alone, suggesting enhanced induction of functional antibodies. In addition, imiquimod-adjuvanted vaccine induced a robust IFN-γ cellular response. These responses correlated with improved protection compared to influenza subunit vaccine alone, as well as reduced viral replication and production of pro-inflammatory cytokines in the lungs. The finding that microneedle delivery of imiquimod with influenza subunit vaccine induces improved immune responses compared to vaccine alone supports the use of TLR7 ligands as adjuvants for skin-based influenza vaccines. |
| doi_str_mv | 10.1371/journal.pone.0041501 |
| format | Article |
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Here we investigate the use of TLR ligands as adjuvants with skin-based delivery of influenza subunit vaccine. BALB/c mice received 1 µg of monovalent H1N1 subunit vaccine alone or with 1 µg of imiquimod or poly(I:C) individually or in combination via coated microneedle patches inserted into the skin. Poly(I:C) adjuvanted subunit influenza vaccine induced similar antigen-specific immune responses compared to vaccine alone when delivered to the skin by microneedles. However, imiquimod-adjuvanted vaccine elicited higher levels of serum IgG2a antibodies and increased hemagglutination inhibition titers compared to vaccine alone, suggesting enhanced induction of functional antibodies. In addition, imiquimod-adjuvanted vaccine induced a robust IFN-γ cellular response. These responses correlated with improved protection compared to influenza subunit vaccine alone, as well as reduced viral replication and production of pro-inflammatory cytokines in the lungs. The finding that microneedle delivery of imiquimod with influenza subunit vaccine induces improved immune responses compared to vaccine alone supports the use of TLR7 ligands as adjuvants for skin-based influenza vaccines.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0041501</identifier><identifier>PMID: 22848514</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adjuvants ; Adjuvants, Immunologic - pharmacology ; Aluminum ; Aminoquinolines - immunology ; Aminoquinolines - pharmacology ; Animals ; Antibodies ; Antibodies, Viral - immunology ; Antigens ; Antiviral Agents - immunology ; Antiviral Agents - pharmacology ; B cells ; Biology ; Coating effects ; Cytokines ; Dendritic cells ; Drug delivery systems ; Drug dosages ; Female ; Hemagglutination inhibition ; Imiquimod ; Immune response ; Immunization ; Immunoglobulin G ; Immunoglobulin G - immunology ; Immunoglobulins ; Immunology ; Inflammation ; Influenza ; Influenza A Virus, H1N1 Subtype - immunology ; Influenza vaccines ; Influenza Vaccines - immunology ; Influenza Vaccines - pharmacology ; Injections, Intradermal ; Interferon ; Ligands ; Lungs ; Medical research ; Medicine ; Mice ; Mice, Inbred BALB C ; Needles ; Pandemics ; Peptides ; Poly I-C - immunology ; Poly I-C - pharmacology ; Polyinosinic:polycytidylic acid ; Skin ; Streptococcus ; Surveillance ; TLR7 protein ; Toll-like receptors ; Vaccination ; Vaccines ; Vaccines, Subunit - immunology ; Vaccines, Subunit - pharmacology ; Viruses ; γ-Interferon</subject><ispartof>PloS one, 2012-07, Vol.7 (7), p.e41501-e41501</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Weldon et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://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 investigate the use of TLR ligands as adjuvants with skin-based delivery of influenza subunit vaccine. BALB/c mice received 1 µg of monovalent H1N1 subunit vaccine alone or with 1 µg of imiquimod or poly(I:C) individually or in combination via coated microneedle patches inserted into the skin. Poly(I:C) adjuvanted subunit influenza vaccine induced similar antigen-specific immune responses compared to vaccine alone when delivered to the skin by microneedles. However, imiquimod-adjuvanted vaccine elicited higher levels of serum IgG2a antibodies and increased hemagglutination inhibition titers compared to vaccine alone, suggesting enhanced induction of functional antibodies. In addition, imiquimod-adjuvanted vaccine induced a robust IFN-γ cellular response. These responses correlated with improved protection compared to influenza subunit vaccine alone, as well as reduced viral replication and production of pro-inflammatory cytokines in the lungs. 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Here we investigate the use of TLR ligands as adjuvants with skin-based delivery of influenza subunit vaccine. BALB/c mice received 1 µg of monovalent H1N1 subunit vaccine alone or with 1 µg of imiquimod or poly(I:C) individually or in combination via coated microneedle patches inserted into the skin. Poly(I:C) adjuvanted subunit influenza vaccine induced similar antigen-specific immune responses compared to vaccine alone when delivered to the skin by microneedles. However, imiquimod-adjuvanted vaccine elicited higher levels of serum IgG2a antibodies and increased hemagglutination inhibition titers compared to vaccine alone, suggesting enhanced induction of functional antibodies. In addition, imiquimod-adjuvanted vaccine induced a robust IFN-γ cellular response. These responses correlated with improved protection compared to influenza subunit vaccine alone, as well as reduced viral replication and production of pro-inflammatory cytokines in the lungs. The finding that microneedle delivery of imiquimod with influenza subunit vaccine induces improved immune responses compared to vaccine alone supports the use of TLR7 ligands as adjuvants for skin-based influenza vaccines.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22848514</pmid><doi>10.1371/journal.pone.0041501</doi><tpages>e41501</tpages><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_plos_journals_1327116882 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adjuvants Adjuvants, Immunologic - pharmacology Aluminum Aminoquinolines - immunology Aminoquinolines - pharmacology Animals Antibodies Antibodies, Viral - immunology Antigens Antiviral Agents - immunology Antiviral Agents - pharmacology B cells Biology Coating effects Cytokines Dendritic cells Drug delivery systems Drug dosages Female Hemagglutination inhibition Imiquimod Immune response Immunization Immunoglobulin G Immunoglobulin G - immunology Immunoglobulins Immunology Inflammation Influenza Influenza A Virus, H1N1 Subtype - immunology Influenza vaccines Influenza Vaccines - immunology Influenza Vaccines - pharmacology Injections, Intradermal Interferon Ligands Lungs Medical research Medicine Mice Mice, Inbred BALB C Needles Pandemics Peptides Poly I-C - immunology Poly I-C - pharmacology Polyinosinic:polycytidylic acid Skin Streptococcus Surveillance TLR7 protein Toll-like receptors Vaccination Vaccines Vaccines, Subunit - immunology Vaccines, Subunit - pharmacology Viruses γ-Interferon |
| title | Effect of adjuvants on responses to skin immunization by microneedles coated with influenza subunit vaccine |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T04%3A07%3A18IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Effect%20of%20adjuvants%20on%20responses%20to%20skin%20immunization%20by%20microneedles%20coated%20with%20influenza%20subunit%20vaccine&rft.jtitle=PloS%20one&rft.au=Weldon,%20William%20C&rft.date=2012-07-25&rft.volume=7&rft.issue=7&rft.spage=e41501&rft.epage=e41501&rft.pages=e41501-e41501&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0041501&rft_dat=%3Cgale_plos_%3EA477044885%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1327116882&rft_id=info:pmid/22848514&rft_galeid=A477044885&rft_doaj_id=oai_doaj_org_article_64fbf7d8229249eeb0167bf3d49491d8&rfr_iscdi=true |