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

• Type of Material: Article
• Authors: Elizabeth Q. Littauer, Emory University; Lisa K. Mills, Emory University; Nicole Brock, Emory University; E. Stein Esser, Emory University; Andrey Romanyuk, Georgia Institute of Technology; Joanna A. Pulit-Penaloza, Emory University; Elena V. Vassilieva, Emory University; Jacob T. Beaver, Emory University; Olivia Antao, Emory University; Florian Krammer, Icahn School of Medicine at Mount Sinai; Richard W Compans, Emory University; Mark R. Prausnitz, Emory University; Ioanna Skountzou, Emory University
• Language: English
• Date: 2018-04-28
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2018 The Authors.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.jconrel.2018.02.033
• Title of Journal or Parent Work: Journal of Controlled Release
• ISSN: 0168-3659
• Volume: 276
• Start Page: 1
• End Page: 16
• Grant/Funding Information: This work was supported by NIH grant 5R01AI111557.
• Keywords: Chemistry; COLONY-STIMULATING FACTOR; DRUG-DELIVERY; VIRUS INFECTION; IMMUNIZATION; Pharmacology & Pharmacy; Life Sciences & Biomedicine; Physical Sciences; PROTECTIVE IMMUNE-RESPONSES; ADJUVANT; EXPRESSION; Adjuvant; DENDRITIC CELLS; Microneedle; GM-CSF; IMMUNOGENICITY; Chemistry, Multidisciplinary; Skin; Science & Technology; Co-delivery; T-CELL RESPONSES; Influenza
• Research Categories: Engineering, Chemical; Health Sciences, Immunology; Biology, Microbiology

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.