Changes in human Langerhans cells following intradermal injection of influenza virus-like particle vaccines.
There is a significant gap in our fundamental understanding of early morphological and migratory changes in human Langerhans cells (LCs) in response to vaccine stimulation. As the vast majority of LCs studies are conducted in small animal models, substantial interspecies variation in skin architecture and immunity must be considered when extrapolating the results to humans. This study aims to determine whether excised human skin, maintained viable in organ culture, provides a useful human model for measuring and understanding early immune response to intradermally delivered vaccine candidates. Excised human breast skin was maintained viable in air-liquid-interface organ culture. This model was used for the first time to show morphological changes in human LCs stimulated with influenza virus-like particle (VLP) vaccines delivered via intradermal injection. Immunohistochemistry of epidermal sheets and skin sections showed that LCs in VLP treated skin lost their typical dendritic morphology. The cells were more dispersed throughout the epidermis, often in close proximity to the basement membrane, and appeared vertically elongated. Our data provides for increased understanding of the complex morphological, spatial and temporal changes that occur to permit LC migration through the densely packed keratinocytes of the epidermis following exposure to vaccine. Significantly, the data not only supports previous animal data but also provides new and essential evidence of host response to this vaccination strategy in the real human skin environment.
Pearton
Marc
M
Welsh School of Pharmacy, Cardiff University, Cardiff, United Kingdom.
Kang
Sang-Moo
SM
Song
Jae-Min
JM
Anstey
Alexander V
AV
Ivory
Matthew
M
Compans
Richard W
RW
Birchall
James C
JC
D016367:Baculoviridae / Q000276:immunology*; D002452:Cell Count; D004817:Epidermis / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype; D007271:Injections, Intradermal; D007801:Langerhans Cells / Q000166:cytology* / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000276:immunology*
D014765:Viral Vaccines
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