COVID-19
Immunogenicity and tolerability of COVID-19 messenger RNA vaccines in primary immunodeficiency patients with functional B-cell defects

https://doi.org/10.1016/j.jaci.2021.11.022Get rights and content

Background

Data on the safety and efficacy of coronavirus disease 2019 (COVID-19) vaccination in people with a range of primary immunodeficiencies (PIDs) are lacking because these patients were excluded from COVID-19 vaccine trials. This information may help in clinical management of this vulnerable patient group.

Objective

We assessed humoral and T-cell immune responses after 2 doses of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccines in patients with PID and functional B-cell defects.

Methods

A double-center retrospective review was performed of patients with PID who completed COVID-19 mRNA vaccination and who had humoral responses assessed through SARS-CoV-2 spike protein receptor binding domain (RBD) IgG antibody levels with reflex assessment of the antibody to block RBD binding to angiotensin-converting enzyme 2 (ACE2; hereafter referred to as ACE2 receptor blocking activity, as a surrogate test for neutralization) and T-cell response evaluated by an IFN-γ release assay. Immunization reactogenicity was also reviewed.

Results

A total of 33 patients with humoral defect were evaluated; 69.6% received BNT162b2 vaccine (Pfizer-BioNTech) and 30.3% received mRNA-1273 (Moderna). The mRNA vaccines were generally well tolerated without severe reactions. The IFN-γ release assay result was positive in 24 (77.4%) of 31 patients. Sixteen of 33 subjects had detectable RBD-specific IgG responses, but only 2 of these 16 subjects had an ACE2 receptor blocking activity level of ≥50%.

Conclusion

Vaccination of this cohort of patients with PID with COVID-19 mRNA vaccines was safe, and cellular immunity was stimulated in most subjects. However, antibody responses to the spike protein RBD were less consistent, and, when detected, were not effective at ACE2 blocking.

Key words

SARS-CoV-2
SARS-CoV-2 vaccination
primary immunodeficiency
ACE2 blocking antibody
SARS-CoV-2 spike protein antibody
antibody deficiency
common variable immunodeficiency
Good syndrome
mAb
SARS-CoV-2 IFN-γ release assay

Abbreviations used

ACE2
Angiotensin-converting enzyme 2
COVID-19
Coronavirus disease 2019
CTLA-4
Cytotoxic T lymphocyte–associated protein 4
CVID
Common variable immunodeficiency
ELISA
Enzyme-linked immunosorbent assay
EUA
Emergency use authorization
IGRA
IFN-γ release assay
IVIG
Intravenous immunoglobulin
mRNA
Messenger RNA
PID
primary immunodeficiency
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2

Cited by (0)

The last 2 authors contributed equally to this article, and both should be considered senior author.

Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest.

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