Intradermal skin test with mRNA vaccines as a surrogate marker of T cell immunity in immunocompromised patients - 10/07/23

Doi : 10.1016/j.jinf.2023.06.005

Benedict Fallet ^a,^{^{1
Co-first author.},}^{^{2
https://orcid.org/0000-0003-1530-6355.}}, Mathilde Foglierini ^a,^b,^{^{1
Co-first author.},}^{^{3
https://orcid.org/0000-0001-7538-4262.}}, Raphael Porret ^a,^{^{4
https://orcid.org/0009-0007-2781-9250.}}, Ana Alcaraz-Serna ^a,^{^{5
https://orcid.org/0000-0002-9452-6788.}}, Christophe Sauvage ^c, Raphael Jenelten ^d,^{^{6
https://orcid.org/0000-0002-0122-8918.}}, Teofila Caplanusi ^d, Michel Gilliet ^d,^e,^{^{7
https://orcid.org/0000-0002-4609-3762.}}, Laurent Perez ^a,^e,^{^{8
https://orcid.org/0000-0002-8860-7928.}}, Craig Fenwick ^a,^{^{9
https://orcid.org/0000-0002-9435-0110.}}, Raphael Genolet ^c,^{^{10
https://orcid.org/0000-0001-9335-3945.}}, Alexandre Harari ^c,^e,^{^{11
https://orcid.org/0000-0002-1055-2090.}}, Sara Bobisse ^c,^{^{12
https://orcid.org/0000-0002-3502-3224.}}, Raphael Gottardo ^b,^e,^f,^{^{13
https://orcid.org/0000-0002-3867-0232.}}, Giuseppe Pantaleo ^a,^e,^{^{14
https://orcid.org/0000-0003-3743-1317.}}, Yannick D. Muller ^a,^e,^⁎,^{^{15
https://orcid.org/0000-0003-0513-7156.}}
^a Division of Immunology and Allergy, University Hospital of Lausanne, Switzerland
^b Biomedical Data Science Center, University Hospital of Lausanne, Switzerland
^c Center for Cell Immunotherapy, Department of Oncology and Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Lausanne CH-1066, Switzerland
^d Department of Dermatology and Venereology, University Hospital of Lausanne, Switzerland
^e University of Lausanne, Faculty of Biology and Medicine, Lausanne, Switzerland
^f Swiss Institute for Bioinformatics, Lausanne, Switzerland

^⁎Correspondence to: Service d′immunologie et d′allergie, Département de Médecine, BH010-511, Rue du Bugnon 46, CH-1011 Lausanne, Switzerland.Service d′immunologie et d′allergie, Département de MédecineBH010-511, Rue du Bugnon 46LausanneCH-1011Switzerland

Summary

Objectives

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.

Methods

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 24 h after IDT and single-cell RNAseq was performed in three vaccinated volunteers.

Results

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.

Conclusions

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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Highlights

•	Intradermal skin test (IDT) with mRNA COVID-19 vaccines can be used as a surrogate of T cell immunity.
•	COVID-19 mRNA vaccines induce the trafficking of mainly T cells with a memory profile.
•	Seronegative immunocompromised patients with T cell immunity are mainly under B cell-depleting therapy.
•	Seronegative immunocompromised patients without detectable T cell immunity are mainly transplant recipients.

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Keywords : SARS-CoV-2, COVID, T cells, Vaccine, Skin, Immunosuppression

Plan

Study design and population

Serological assays

IFNγ-Elispot

Intradermal skin test (IDT)

Skin biopsies and cell sorting

10X single-cell RNA and TCR sequencing analysis

HLA genotyping

CRediT authorship contribution statement

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Vol 87 - N° 2

P. 111-119 - août 2023 Retour au numéro

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Intradermal skin test with mRNA vaccines as a surrogate marker of T cell immunity in immunocompromised patients - 10/07/23

Summary

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Methods

Results

Conclusions

Highlights

Plan

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