Immunogenicity and tolerability of COVID-19 messenger RNA vaccines in primary immunodeficiency patients with functional B-cell defects - 18/01/22

Doi : 10.1016/j.jaci.2021.11.022

Michele N. Pham, MD ^a, Kanagavel Murugesan, PhD ^b, Niaz Banaei, MD ^b,^c,^e, Benjamin A. Pinsky, MD, PhD ^b,^c,^f, Monica Tang, MD ^a, Elisabeth Hoyte, NP ^d, David B. Lewis, MD ^d, Yael Gernez, MD, PhD ^d,^⁎
^a Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, Department of Internal Medicine, University of California, San Francisco, Calif
^b Department of Pathology, Stanford University School of Medicine, Stanford, Calif
^c Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, Calif
^d Division of Allergy, Immunology and Rheumatology, Department of Pediatrics, Stanford University School of Medicine, Stanford, Calif
^e Clinical Microbiology Laboratory, Stanford Health Care, Stanford, Calif
^f Clinical Virology Laboratory, Stanford Health Care, Stanford, Calif

^∗Corresponding author: Yael Gernez, MD, PhD, Department of Pediatrics, Division of Allergy, Immunology, and Rheumatology, Stanford University School of Medicine, 269 Campus Dr, CCSR Ste 3215, Stanford, CA 94305-5366.Department of PediatricsDivision of AllergyImmunology, and RheumatologyStanford University School of Medicine269 Campus DrCCSR Ste 3215StanfordCA94305-5366

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Abstract

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.

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Graphical abstract

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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, COVID-19, CTLA-4, CVID, ELISA, EUA, IGRA, IVIG, mRNA, PID, SARS-CoV-2

Plan

Results and discussion

	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.