High-dimensional profiling of immune response to vaccines using bio-stabilized and injectable natural human skin.
SCHOLAERT M. 1,2, PERIES M. 2, BRAUN E. 2, MARTIN J. 1, SERHAN N. 1, LOSTE A. 1, BRUNER A. 1, BASSO L. 1, MERLE E. 3, DESCARGUES P. 3, PAGES E. 2, GAUDENZIO N. 1,2
1 Toulouse Institute for Infectious and Inflammatory Diseases (Infinity) INSERM UMR1291 - CNRS UMR5051 - University Toulouse III, Toulouse, France; 2 Genoskin SAS, Toulouse, France; 3 Genoskin Inc, Salem Ma, United States
Vaccines are often developed using a combination of congenic mouse experiments, in vitro culture of human peripheral blood cells and, for some of them, data-driven biosimulation platforms. While such experimental settings have been very useful, they often fail to recapitulate the complexity of the human immune system found in tissue at the site of injection. The skin is composed of structural cells that tightly interact with more than 17 different immune cells to form a unique ecosystem. We have developed a proprietary method to maintain ex vivo human skin biopsies (Hyposkin?) alive, functional and fully immunocompetent for a prolonged period of time. Built on Hyposkin?, we have designed a general framework to study the early steps of human immune responses to vaccines and adjuvants in their natural environment at the site of injection.
Combining 3-D two photon imaging, multiplexed cytokines dosage and single cell RNA sequencing, here we show that 1) both immune and structural compartments in HypoSkin? stay alive and functional for a 10 days period and that 2) the injection of the Moderna vaccine against COVID19 triggers the release of a specific signature of cytokines and chemokine, among which MDC, TARC and MCP-1 well known to be involved in T cells and monocytes recruitment. Finally, 3) the longitudinal single cell analysis of skin-resident immune cells transcriptome upon injection showed a time-dependent modulation of myeloid and lymphoid cells activation status, strongly suggesting the generation of a coordinated immune response at the site of injection.
The Hyposkin? platform thus provides a unique framework for the study of the early steps of immune response to drugs in its native environment and, combined with different technologies, it might help to maximize specific immune targeting or evaluate adjuvant potency ahead of clinical trials.