Stable incorporation of GM-CSF into dissolvable microneedle patch improves skin vaccination against influenza
| Autor: | Ioanna Skountzou, Florian Krammer, E. Stein Esser, Andrey V. Romanyuk, Mark R. Prausnitz, Olivia Q Antao, Joanna A. Pulit-Penaloza, Richard W. Compans, Nicole Brock, Jacob T Beaver, Elena V. Vassilieva, Lisa Mills, Elizabeth Q. Littauer |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Injections Intradermal Microinjections Influenza vaccine medicine.medical_treatment Pharmaceutical Science Transdermal Patch Administration Cutaneous Virus Article Madin Darby Canine Kidney Cells 03 medical and health sciences 0302 clinical medicine Dogs Influenza A Virus H1N1 Subtype Orthomyxoviridae Infections medicine Animals Memory B cell Mice Inbred BALB C business.industry Immunogenicity Influenza A Virus H3N2 Subtype Vaccination Granulocyte-Macrophage Colony-Stimulating Factor medicine.disease 030104 developmental biology Immunization Influenza Vaccines Needles 030220 oncology & carcinogenesis Immunology Female Skin cancer business Adjuvant |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|