Easy approach to detect cell immunity to COVID vaccines in common variable immunodeficiency patients

Main Article Content

Yvelise Barrios
Andrés Franco
Cristina Alava-Cruz
Ricardo Cuesta-Martin
Carmen Camara
Victor Matheu

Keywords

Common Variable Immunodeficiency (CVID), rare disease, T-cell response, COVID vaccination, DTH, skin test, SARS-CoV-2, antibody deficiency

Abstract

Background: Patients with primary antibody deficiencies, such as Common Variable Immunodeficiency (CVID), have some problems to assess immune response after coronavirus disease (COVID) vaccination. Cutaneous delayed-type hypersensitivity (DTH) has the potential to be used as a useful, simple, and cheaper tool to assess T-cell (T lymphocyte) function.


Methods: Seventeen patients with CVID, a rare disease, received two doses of the mRNA-based Pfizer-BioNTech COVID-19 vaccine. Humoral Immune Response (HIR) was determined by measuring specific immunoglobulin G (IgG) antibodies, and Cellular Immune Response (CIR) was evaluated using an ex vivo interferon-gamma release assay (IGRA) and in vivo by DTH skin test.


Results: Two weeks after the second dose of the vaccine, 12 out of 17 CVID patients have high optical density (OD) ratios of specific anti-spike protein (S) IgG whereas five patients were negative or low. Ex vivo CIR was considered positive in 14 out of 17 S1-stimulated patients. Unspecific stimulation was positive in all 17 patients showing no T-cell defect. A positive DTH skin test was observed in 16 CVID patients. The only patient with negative DTH also had negative ex vivo CIR.


Conclusions: The use of DTH to evaluate CIR was validated with an optimal correlation with the ex vivo CIR. The CIR after vaccination in patients with antibody deficiencies seems to have high precision and more sensitivity to antibodies-based methods in CVID.


Clinical Implications: There is a remarkable correlation between cutaneous DTH and ex vivo IGRA after COVID vaccination. A COVID-specific skin DTH test could be implemented in large populations.


Capsule Summary: Cutaneous delayed-type hypersensitivity has the potential to be used as a useful, simple, and cheaper tool to assess T-cell functioning.

Abstract 161 | PDF Downloads 214 HTML Downloads 10 XML Downloads 4

References

1. Sandbrink JB, Shattock RJ. RNA vaccines: A suitable platform for tackling emerging pandemics? Front Immunol. 2020 Dec 22;11:608460. 10.3389/fimmu.2020.608460. PMid: 33414790; PMCID: PMC7783390.

2. Hagin D, Freund T, Navon M, Halperin T, Adir D, Marom R, et al. Immunogenicity of Pfizer-BioNTech COVID-19 vaccine in patients with inborn errors of immunity. J Allergy Clin Immunol. 2021 Jun 1:S0091-6749(21)00887-3. Epub ahead of print. 10.1016/j.jaci.2021.05.029. PMid: 34087242; PMCID: PMC8168345.

3. Barrios Y, Franco A, Sanchez-Machin I, Poza-Guedes P, Gonzalez-Perez R, Matheu V. A novel application of delayed-type hipersensitivity reaction to measure cellular immune response in SARS-CoV-2 exposed individuals. Clin Immunol. 2021 May;226:108730. Epub 2021 Apr 16. 10.1016/j.clim.2021.108730. PMid: 33865990; PMCID: PMC8049849.

4. Barrios Y, Franco A, Sánchez-Machín I, Poza-Guedes P, González-Pérez R, Matheu V. The beauty of simplicity: Delayed-type hypersensitivity reaction to measure cellular immune responses in RNA-SARS-Cov-2 vaccinated individuals. Vaccines. 2021;9:575. 10.3390/vaccines9060575.

5. Murugesan K, Jagannathan P, Pham TD, Pandey S, Bonilla HF, Jacobson K, et al. Interferon-gamma release assay for accurate detection of SARS-CoV-2 T cell response. Clin Infect Dis. 2020 Oct 9:ciaa1537. Epub ahead of print. 10.1093/cid/ciaa1537. PMid: 33035306; PMCID: PMC7665338.

6. Hellerstein M. What are the roles of antibodies versus a durable, high quality T-cell response in protective immunity against SARS-CoV-2? Vaccine X. 2020 Dec 11;6:100076. Epub 2020 Aug 28. 10.1016/j.jvacx.2020.100076. PMid: 32875286; PMCID: PMC7452821.

7. Sauer K, Harris T. An effective COVID-19 vaccine needs to engage T cells. Front Immunol. 2020 Sep 28;11:581807. 10.3389/fimmu.2020.581807. PMid: 33117391; PMCID: PMC7549399