Intradermal skin test with mRNA vaccines as a surrogate marker of T cell immunity in immunosuppressed patients

ABSTRACT: The role of T cell immunity in protection against COVID-19 in immunocompromised patients (ICp) who failed to mount serological responses remains ill-defined. Intradermal skin test (IDT) with mRNA vaccines may represent a simple, reliable and affordable tool to measure T cell response in seronegative patients.We compared anti-SARS-CoV-2 antibodies and cellular responses in vaccinated ICp (n=58), healthy seronegative naive controls (NC, n=8), and healthy seropositive vaccinated controls (VC, n=32) by Luminex, spike-induced IFN-γ ELIPSOT and an IDT 3 to 6 months after vaccination. ICp regrouped 18 transplant recipients, 33 individuals with autoimmune diseases, and eight patients with primary immunodeficiencies. In three vaccinated volunteers, we performed a skin biopsy 24h after IDT and single-cell RNAseq of the skin-infiltrating CD45+ cells. Twenty-five percent of seronegative NC had a positive ELIPSOT (2/8) and IDT (1/4), compared to 95% (20/21) and 93% (28/30) in seropositive VC, respectively. Single-cell RNA seq data of positive IDT consistently showed a mixed population of helper and cytotoxic T cells composed of memory T cells in 87%. The TCR repertoire of infiltrating skin lymphocytes revealed 18/1218 clonotypes with known specificities against SARS-CoV-2, among which six were spike-specific. Seronegative ICp with positive Elispot and IDT were in the majority treated with B cell-depleting reagents only, while those with negative IDT were all transplant recipients. Our results indicate that local reaction to IDR is mainly composed of memory T cells and includes SARS-CoV-2-specific T cells, opening the perspective to use IDT as a correlate of protection in immunosuppressed patients.

ORGANISM(S): Homo sapiens

PROVIDER: GSE224028 | GEO | 2023/06/14

REPOSITORIES: GEO