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In this study, we investigated the immune responses after one or two doses of intramuscular or intranasal whole inactivated influenza H5N1 virus vaccine in <jats:styled-content style=\"fixed-case\">BALB<\/jats:styled-content>\/c mice. Serum samples and nasal washings were collected weekly post\u2010vaccination and analysed using enzyme\u2010linked immunosorbent assay (<jats:styled-content style=\"fixed-case\">ELISA<\/jats:styled-content>). Sera were also analysed by the haemagglutination inhibition (<jats:styled-content style=\"fixed-case\">HI<\/jats:styled-content>) assay. Antibody\u2010secreting cells were measured in lymphocytes from spleen and bone marrow via enzyme\u2010linked immunospot (<jats:styled-content style=\"fixed-case\">ELISPOT<\/jats:styled-content>). Splenocytes were stimulated <jats:italic>in vitro,<\/jats:italic> and T\u2010helper profiles were measured through multiplex bead assay in the supernatants, or intracellularly by multiparametric flow cytometry. Both vaccine routes induced high <jats:styled-content style=\"fixed-case\">HI<\/jats:styled-content> titres following the second immunization (intramuscular\u00a0=\u00a0370, intranasal\u00a0=\u00a0230). Moreover, the intramuscular group showed significantly higher levels of serum IgG (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01), IgG1 (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01) and IgG2a (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01) following the second vaccine dose, while the intranasal group exhibited significantly higher levels of serum IgA (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) and local IgA (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01) in the nasal washings. Also, IgA antibody\u2010secreting cells were found in significantly higher numbers in the intranasal group in both the spleen (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01) and the bone marrow (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01). Moreover, Th1 (<jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u2010<jats:italic>\u03b1<\/jats:italic>,<jats:styled-content style=\"fixed-case\"> IL<\/jats:styled-content>\u20102, <jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>\u2010<jats:italic>\u03b3<\/jats:italic>) and Th2 (<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20104, <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20105, <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201010) cytokines were expressed by both groups, yet only the intranasal group expressed the Th17 marker <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201017. As the intranasal vaccines induce local IgA and are easily administered, we suggest the intranasally administered whole virus vaccine as a promising candidate for a pandemic H5N1 vaccine.<\/jats:p>","DOI":"10.1111\/sji.12288","type":"journal-article","created":{"date-parts":[[2015,3,2]],"date-time":"2015-03-02T19:27:26Z","timestamp":1425324446000},"page":"305-317","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Induction of Local Secretory IgA and Multifunctional <scp>CD<\/scp>4<sup>+<\/sup> T\u2010helper Cells Following Intranasal Immunization with a H5N1 Whole Inactivated Influenza Virus Vaccine in <scp>BALB<\/scp>\/c Mice"],"prefix":"10.1111","volume":"81","author":[{"given":"M.","family":"Trondsen","sequence":"first","affiliation":[{"name":"The Influenza Centre Department of Clinical Science University of Bergen Bergen Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. A.","family":"Aqrawi","sequence":"additional","affiliation":[{"name":"The Influenza Centre Department of Clinical Science University of Bergen Bergen Norway"},{"name":"Jebsen Centre for Influenza Vaccine Research University of Bergen Bergen Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Zhou","sequence":"additional","affiliation":[{"name":"The Influenza Centre Department of Clinical Science University of Bergen Bergen Norway"},{"name":"Jebsen Centre for Influenza Vaccine Research University of Bergen Bergen Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Pedersen","sequence":"additional","affiliation":[{"name":"The Influenza Centre Department of Clinical Science University of Bergen Bergen Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. C.","family":"Trieu","sequence":"additional","affiliation":[{"name":"The Influenza Centre Department of Clinical Science University of Bergen Bergen Norway"},{"name":"Jebsen Centre for Influenza Vaccine Research University of Bergen Bergen Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Zhou","sequence":"additional","affiliation":[{"name":"Unit of Antiviral Immunity and Genetic Therapy Institute Pasteur of Shanghai Chinese Academy of Sciences Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. 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