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J Control Release. 2018 Feb 26;276:1-16. doi: 10.1016/j.jconrel.2018.02.033. [Epub ahead of print]
Stable incorporation of GM-CSF into dissolvable microneedle patch improves skin vaccination against influenza.
Littauer EQ1, Mills LK1, Brock N1, Esser ES1, Romanyuk A2, Pulit-Penaloza JA1, Vassilieva EV1, Beaver JT1, Antao O1, Krammer F3, Compans RW1, Prausnitz MR2, Skountzou I4.
Author information
Abstract
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.
KEYWORDS:
Adjuvant; Co-delivery; GM-CSF; Influenza; Microneedle; Skin
PMID: 29496540 DOI: 10.1016/j.jconrel.2018.02.033
Stable incorporation of GM-CSF into dissolvable microneedle patch improves skin vaccination against influenza.
Littauer EQ1, Mills LK1, Brock N1, Esser ES1, Romanyuk A2, Pulit-Penaloza JA1, Vassilieva EV1, Beaver JT1, Antao O1, Krammer F3, Compans RW1, Prausnitz MR2, Skountzou I4.
Author information
Abstract
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.
KEYWORDS:
Adjuvant; Co-delivery; GM-CSF; Influenza; Microneedle; Skin
PMID: 29496540 DOI: 10.1016/j.jconrel.2018.02.033