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Intranasal nanoemulsion vaccine confers long‐lasting immunomodulation and sustained unresponsiveness in a murine model of milk allergy
dc.contributor.authorO’Konek, Jessica J.
dc.contributor.authorLanders, Jeffrey J.
dc.contributor.authorJanczak, Katarzyna W.
dc.contributor.authorLindsey, Hayley K.
dc.contributor.authorMondrusov, Anna M.
dc.contributor.authorTotten, Tiffanie D.
dc.contributor.authorBaker, James R.
dc.date.accessioned2020-05-05T19:36:29Z
dc.date.availableWITHHELD_12_MONTHS
dc.date.available2020-05-05T19:36:29Z
dc.date.issued2020-04
dc.identifier.citationO’Konek, Jessica J.; Landers, Jeffrey J.; Janczak, Katarzyna W.; Lindsey, Hayley K.; Mondrusov, Anna M.; Totten, Tiffanie D.; Baker, James R. (2020). "Intranasal nanoemulsion vaccine confers long‐lasting immunomodulation and sustained unresponsiveness in a murine model of milk allergy." Allergy 75(4): 872-881.
dc.identifier.issn0105-4538
dc.identifier.issn1398-9995
dc.identifier.urihttps://hdl.handle.net/2027.42/154959
dc.description.abstractBackgroundImmunotherapy for food allergy requires prolonged treatment protocols and, in most cases, does not lead to durable modulation of the allergic immune response. We have demonstrated an intranasal (IN) nanoemulsion adjuvant that redirects allergen‐specific Th2 responses toward Th1 and Th17 immunity, and protects from allergen challenge after only 2‐4 monthly administrations. Here, we investigate the ability of this technology to provide long‐term modulation of allergy in a murine model of cow’s milk allergy.MethodsSix weeks after sensitization to bovine casein, mice received four, monthly IN immunizations with nanoemulsion formulated with casein. Protection from casein challenge was assessed at 4 and 16 weeks after the final vaccine administration.ResultsThe NE vaccine significantly blunted the physiological responses to allergen challenge, and this effect persisted for at least 16 weeks. The protection from challenge was associated with the suppression of casein‐specific Th2 immunity and induced Th1 and Th17 cytokines as well as induction of IL‐10. Of interest, while immunized animals showed significantly decreased Th2 cytokine responses, cow’s milk‐specific IgE remained elevated in the serum at levels associated with reactivity in control sensitized animals. Protection was associated with suppressed mast cell activation and markedly reduced mast cell infiltration into the small intestine.ConclusionThe sustained unresponsiveness of at least 16 weeks after vaccination suggests that the nanoemulsion vaccine alters the allergic phenotype in a persistent manner different from traditional desensitization, and this leads to long‐term suppressive effects on allergic disease without eliminating serum IgE.This study evaluates the ability of an intranasal nanoemulsion‐based vaccine to induce long‐term modulation of allergic reactions in a mouse model of cow’s milk allergy. Intranasal immunization with nanoemulsion adjuvant suppresses Th2 responses and anaphylaxis. The sustained unresponsiveness of at least 16 weeks after vaccination suggests that the nanoemulsion vaccine alters the allergic phenotype.
dc.publisherWiley Periodicals, Inc.
dc.subject.otherallergy treatment
dc.subject.otherimmunotherapy and tolerance induction
dc.subject.otherimmunotherapy vaccines and mechanisms
dc.subject.othervaccines
dc.subject.otherfood allergy
dc.titleIntranasal nanoemulsion vaccine confers long‐lasting immunomodulation and sustained unresponsiveness in a murine model of milk allergy
dc.typeArticle
dc.rights.robotsIndexNoFollow
dc.subject.hlbsecondlevelMicrobiology and Immunology
dc.subject.hlbtoplevelHealth Sciences
dc.description.peerreviewedPeer Reviewed
dc.description.bitstreamurlhttps://deepblue.lib.umich.edu/bitstream/2027.42/154959/1/all14064_am.pdf
dc.description.bitstreamurlhttps://deepblue.lib.umich.edu/bitstream/2027.42/154959/2/all14064.pdf
dc.description.bitstreamurlhttps://deepblue.lib.umich.edu/bitstream/2027.42/154959/3/all14064-sup-0003-FigS3.pdf
dc.identifier.doi10.1111/all.14064
dc.identifier.sourceAllergy
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dc.owningcollnameInterdisciplinary and Peer-Reviewed


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