The immunologically active microenvironment and the high density of antigen-presenting cells make the skin an attractive target for vaccination. The use of microarray patches to deliver vaccines directly these layers of the skin presents a promising alternative to traditional vaccine delivery mechanisms. One such microarray patch is the Vaxxas High-Density Microarray patch (HD-MAP). Delivery of vaccines via the HD-MAP has shown dramatic improvements in immunogenicity in terms of magnitude, breadth and quality of the immune response. Here, we aim to further understand these immune responses using novel transcriptomic techniques.
We used newly available spatial transcriptomics tools (10x Visium and Xenium) on skin biopsies from the HD-MAP application site to examine the immunological mechanisms underpinning the immune enhancement phenomena associated with HD-MAP vaccine delivery. We also used single-cell sequencing of B cells from mice vaccinated with a SARS-CoV-2 spike protein vaccine via the intradermal or HD-MAP routes to further understand the functional immune outcomes.
Spatial transcriptomic analysis of the HD-MAP application site revealed rapid triggering of a localized enhanced inflammatory state in the skin, characterized by multiple inflammatory signaling pathways, resulting in rapid infiltration of multiple immune cells. The B-cell repertoire analysis showed that HD-MAP vaccination produces populations of antibodies of greater diversity than intradermal injection. Analysis of recombinantly-expressed antibody clones revealed antibodies isolated from HD-MAP vaccinated animals showed enhanced neutralization capacity against multiple SARS-CoV-2 virus variants compared to those derived from intradermal vaccination. This work provides unprecedented detail into the precise transcriptional mechanisms and functional antibody responses following HD-MAP vaccination.