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Immunogenicity and tolerability of COVID-19 messenger RNA vaccines in primary immunodeficiency patients with functional B-cell defects.
J Allergy Clin Immunol. 2022 03; 149(3):907-911.e3.JA

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.

Links

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Authors+Show Affiliations

Pham MN
Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, Department of Internal Medicine, University of California, San Francisco, Calif.
Murugesan K
Department of Pathology, Stanford University School of Medicine, Stanford, Calif.
Banaei N
Department of Pathology, Stanford University School of Medicine, Stanford, Calif; Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, Calif; Clinical Microbiology Laboratory, Stanford Health Care, Stanford, Calif.
Pinsky BA
Department of Pathology, Stanford University School of Medicine, Stanford, Calif; Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, Calif; Clinical Virology Laboratory, Stanford Health Care, Stanford, Calif.
Tang M
Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, Department of Internal Medicine, University of California, San Francisco, Calif.
Hoyte E
Division of Allergy, Immunology and Rheumatology, Department of Pediatrics, Stanford University School of Medicine, Stanford, Calif.
Lewis DB
Division of Allergy, Immunology and Rheumatology, Department of Pediatrics, Stanford University School of Medicine, Stanford, Calif.
Gernez Y
Division of Allergy, Immunology and Rheumatology, Department of Pediatrics, Stanford University School of Medicine, Stanford, Calif. Electronic address: yaelg@stanford.edu.

MeSH

2019-nCoV Vaccine mRNA-1273AdultAgedAntibodies, ViralB-LymphocytesBNT162 VaccineCOVID-19FemaleHumansImmunity, CellularImmunity, HumoralImmunoglobulin GMaleMiddle AgedPrimary Immunodeficiency DiseasesRetrospective StudiesSARS-CoV-2Spike Glycoprotein, CoronavirusT-LymphocytesYoung Adult

Pub Type(s)

Journal Article
Multicenter Study

Language

eng

PubMed ID

34952033

Citation

Pham, Michele N., et al. "Immunogenicity and Tolerability of COVID-19 Messenger RNA Vaccines in Primary Immunodeficiency Patients With Functional B-cell Defects." The Journal of Allergy and Clinical Immunology, vol. 149, no. 3, 2022, pp. 907-911.e3.
Pham MN, Murugesan K, Banaei N, et al. Immunogenicity and tolerability of COVID-19 messenger RNA vaccines in primary immunodeficiency patients with functional B-cell defects. J Allergy Clin Immunol. 2022;149(3):907-911.e3.
Pham, M. N., Murugesan, K., Banaei, N., Pinsky, B. A., Tang, M., Hoyte, E., Lewis, D. B., & Gernez, Y. (2022). Immunogenicity and tolerability of COVID-19 messenger RNA vaccines in primary immunodeficiency patients with functional B-cell defects. The Journal of Allergy and Clinical Immunology, 149(3), 907-e3. https://doi.org/10.1016/j.jaci.2021.11.022
Pham MN, et al. Immunogenicity and Tolerability of COVID-19 Messenger RNA Vaccines in Primary Immunodeficiency Patients With Functional B-cell Defects. J Allergy Clin Immunol. 2022;149(3):907-911.e3. PubMed PMID: 34952033.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Immunogenicity and tolerability of COVID-19 messenger RNA vaccines in primary immunodeficiency patients with functional B-cell defects. AU - Pham,Michele N, AU - Murugesan,Kanagavel, AU - Banaei,Niaz, AU - Pinsky,Benjamin A, AU - Tang,Monica, AU - Hoyte,Elisabeth, AU - Lewis,David B, AU - Gernez,Yael, Y1 - 2021/12/21/ PY - 2021/08/05/received PY - 2021/10/29/revised PY - 2021/11/05/accepted PY - 2021/12/25/pubmed PY - 2022/3/11/medline PY - 2021/12/24/entrez KW - ACE2 blocking antibody KW - Good syndrome KW - SARS-CoV-2 KW - SARS-CoV-2 IFN-γ release assay KW - SARS-CoV-2 spike protein antibody KW - SARS-CoV-2 vaccination KW - antibody deficiency KW - common variable immunodeficiency KW - mAb KW - primary immunodeficiency SP - 907 EP - 911.e3 JF - The Journal of allergy and clinical immunology JO - J Allergy Clin Immunol VL - 149 IS - 3 N2 - 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. SN - 1097-6825 UR - https://www.unboundmedicine.com/medline/citation/34952033/Immunogenicity_and_tolerability_of_COVID_19_messenger_RNA_vaccines_in_primary_immunodeficiency_patients_with_functional_B_cell_defects_ DB - PRIME DP - Unbound Medicine ER -