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2019-03-29Zeitschriftenartikel DOI: 10.25646/6323
Cross-Protective Potential and Protection-Relevant Immune Mechanisms of Whole Inactivated Influenza Virus Vaccines Are Determined by Adjuvants and Route of Immunization
dc.contributor.authorBhide, Yoshita
dc.contributor.authorDong, Wei
dc.contributor.authorGribonika, Inta
dc.contributor.authorVoshart, Daniëlle
dc.contributor.authorMeijerhof, Tjarko
dc.contributor.authorde Vries-Idema, Jacqueline
dc.contributor.authorNorley, Stephen
dc.contributor.authorGuilfoyle, Kate
dc.contributor.authorSkeldon, Sarah
dc.contributor.authorEngelhardt, Othmar G.
dc.contributor.authorBoon, Louis
dc.contributor.authorChristensen, Dennis
dc.contributor.authorLycke, Nils
dc.contributor.authorHuckriede, Anke
dc.date.accessioned2019-10-16T07:57:01Z
dc.date.available2019-10-16T07:57:01Z
dc.date.issued2019-03-29none
dc.identifier.other10.3389/fimmu.2019.00646
dc.identifier.urihttp://edoc.rki.de/176904/6336
dc.description.abstractAdjuvanted whole inactivated virus (WIV) influenza vaccines show promise as broadly protective influenza vaccine candidates. Using WIV as basis we assessed the relative efficacy of different adjuvants by carrying out a head-to-head comparison of the liposome-based adjuvants CAF01 and CAF09 and the protein-based adjuvants CTA1-DD and CTA1-3M2e-DD and evaluated whether one or more of the adjuvants could induce broadly protective immunity. Mice were immunized with WIV prepared from A/Puerto Rico/8/34 (H1N1) virus intramuscularly with or without CAF01 or intranasally with or without CAF09, CTA1-DD, or CTA1-3M2e-DD, followed by challenge with homologous, heterologous or heterosubtypic virus. In general, intranasal immunizations were significantly more effective than intramuscular immunizations in inducing virus-specific serum-IgG, mucosal-IgA, and splenic IFNγ-producing CD4 T cells. Intranasal immunizations with adjuvanted vaccines afforded strong cross-protection with milder clinical symptoms and better control of virus load in lungs. Mechanistic studies indicated that non-neutralizing IgG antibodies and CD4 T cells were responsible for the improved cross-protection while IgA antibodies were dispensable. The role of CD4 T cells was particularly pronounced for CTA1-3M2e-DD adjuvanted vaccine as evidenced by CD4 T cell-dependent reduction of lung virus titers and clinical symptoms. Thus, intranasally administered WIV in combination with effective mucosal adjuvants appears to be a promising broadly protective influenza vaccine candidate.eng
dc.language.isoengnone
dc.publisherRobert Koch-Institut
dc.rights(CC BY 3.0 DE) Namensnennung 3.0 Deutschlandger
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/de/
dc.subjectwhole inactivated virus (WIV) influenza vaccineseng
dc.subjectliposome-based adjuvantseng
dc.subjectprotein-based adjuvantseng
dc.subjectcross protectioneng
dc.subjectnon-neutralizing serum antibodieseng
dc.subjectCD4 T cellseng
dc.subject.ddc610 Medizin und Gesundheitnone
dc.titleCross-Protective Potential and Protection-Relevant Immune Mechanisms of Whole Inactivated Influenza Virus Vaccines Are Determined by Adjuvants and Route of Immunizationnone
dc.typearticle
dc.identifier.urnurn:nbn:de:kobv:0257-176904/6336-8
dc.identifier.doihttp://dx.doi.org/10.25646/6323
dc.type.versionpublishedVersionnone
local.edoc.container-titleFrontiers in Immunologynone
local.edoc.type-nameZeitschriftenartikel
local.edoc.container-typeperiodical
local.edoc.container-type-nameZeitschrift
local.edoc.container-urlhttps://www.frontiersin.org/articles/10.3389/fimmu.2019.00646/fullnone
local.edoc.container-publisher-nameFrontiers Medianone
local.edoc.container-volume10none
local.edoc.container-issue646none
local.edoc.container-reportyear2019none
local.edoc.container-year2019none
local.edoc.container-firstpage1none
local.edoc.container-lastpage13none
local.edoc.rki-departmentInfektionskrankheitennone
dc.description.versionPeer Reviewednone

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