Stable incorporation of GM-CSF into dissolvable microneedle patch improves skin vaccination against influenza

JOURNAL OF CONTROLLED RELEASE

卷:276

Article

Littauer, Elizabeth Q.¹  Mills, Lisa K.¹  Brock, Nicole¹  Esser, E. Stein¹  Romanyuk, Andrey²  Pulit-Penaloza, Joanna A.¹  Vassilieva, Elena V.¹  Beaver, Jacob T.¹  Antao, Olivia¹  Krammer, Florian³  Compans, Richard W.¹  Prausnitz, Mark R.²  Skountzou, Ioanna¹ 

[1] Emory Univ, Sch Med, Dept Microbiol & Immunol, Emory Vaccine Ctr, 1518 Clifton Rd, Atlanta, GA 30322 USA

[2] Georgia Inst Technol, Sch Chem & Biomol Engn, 311 Ferst Dr, Atlanta, GA 30332 USA

[3] Icahn Sch Med Mt Sinai, Dept Microbiol, 1 Gustave L Levy Pl, New York, NY 10029 USA

关键词: GM-CSF;    Microneedle;    Influenza;    Adjuvant;    Skin;    Co-delivery;   

DOI  :  10.1016/j.jconrel.2018.02.033

来源: Elsevier

【 摘 要 】

The widely used influenza subunit vaccine would benefit from increased protection rates in vulnerable populations. Skin immunization by microneedle (MN) patch can increase vaccine immunogenicity, as well as increase vaccination coverage due to simplified administration. To further increase immunogenicity, we used granulocyte-macrophage colony stimulating factor (GM-CSF), an immunomodulatory cytokine already approved for skin cancer therapy and cancer support treatment. GM-CSF has been shown to be upregulated in skin following MN insertion. The GM-CSF-adjuvanted vaccine induced robust and long-lived antibody responses cross-reactive to homosubtypic and heterosubtypic influenza viruses. Addition of GM-CSF resulted in increased memory B cell persistence relative to groups given influenza vaccine alone and led to rapid lung viral clearance following lethal infection with homologous virus in the mouse model. Here we demonstrate that successful incorporation of the thermolabile cytokine GM-CSF into MN resulted in improved vaccine-induced protective immunity holding promise as a novel approach to improved influenza vaccination. To our knowledge, this is the first successful incorporation of a cytokine adjuvant into dissolvable MNs, thus advancing and diversifying the rapidly developing field of MN vaccination technology.

【 授权许可】

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