Abstract
Intradermal skin test (IDT) with mRNA vaccines may represent a simple, reliable, and affordable tool to measure T cell response in immunocompromised patients who failed to mount serological responses following vaccination with mRNA covid-19 vaccines. We compared anti-SARS-CoV-2 antibodies and cellular responses in vaccinated immunocompromised patients (n=58), healthy seronegative naive controls (NC, n=8), and healthy seropositive vaccinated controls (VC, n=32) by Luminex, spike-induced IFN-γ Elispot and an IDT. A skin biopsy 24h after IDT and single-cell RNAseq was performed in three vaccinated volunteers. Twenty-five percent of seronegative NC had a positive Elispot (2/8) and IDT (1/4), compared to 95% (20/21) and 93% (28/30) in seropositive VC, respectively. Single-cell RNAseq data in the skin of VC showed a predominant mixed population of effector helper and cytotoxic T cells. The TCR repertoire revealed 18/1064 clonotypes with known specificities against SARS-CoV-2, among which six were spike-specific. Seronegative immunocompromised patients with positive Elispot and IDT were in 83% (5/6) treated with B cell-depleting reagents, while those with negative IDT were all transplant recipients. Our results indicate that delayed local reaction to IDT reflects vaccine-induced T-cell immunity opening new perspectives to monitor seronegative patients and elderly populations with waning immunity.
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