Immunogenicity of Pfizer-BioNTech COVID-19 vaccine in patients with inborn errors of immunity

Abstract

Background In mid-December 2020, Israel had started a nationwide mass vaccination campaign against COVID-19. In the first few weeks, medical personnel, elderly citizens and patients with chronic diseases were prioritized. As such, patients with primary and secondary immunodeficiencies were encouraged to receive the vaccine. While the efficacy of RNA-based COVID-19 vaccines was demonstrated in the general population, little is known about their efficacy and safety in patients with Inborn Errors of Immunity (IEI). Objectives To evaluate the humoral and cellular immune response to COVID-19 vaccine in a cohort of IEI patients. Methods 26 adult patients were enrolled, and plasma and peripheral blood mononuclear cells were collected two weeks following the second dose of Pfizer-BioNTech COVID-19 vaccine. Humoral response was evaluated by testing anti-SARS-CoV-2 Spike (S) Receptor Binding Domain (RBD) and anti-Nuclear (N) antibody titers, and evaluation of neutralizing ability by inhibition of RBD:ACE2 binding. Cellular immune response was evaluated by ELISpot, estimating IL2 and IFNγ secretion in response to pooled SARS-CoV-2 S or M peptides. Results Our cohort included 18 patients with predominantly antibody deficiency, 2 with combined immunodeficiency, 3 with immune-dysregulation, and 3 with other genetically defined diagnoses. 22/26 were receiving immunoglobulin replacement therapy. 18/26 developed specific antibody response and 19/26 showed S-peptide specific T-cell response. None of the patients reported significant adverse events. Conclusion Vaccinating IEI patients is safe, and most patients were able to develop vaccine specific antibody response, S-protein specific cellular response or both.

Serological Response in Lung Transplant Recipients after Two Doses of SARS-CoV-2 mRNA Vaccines

“…While this correlation approach may serve as a proxy for neutralization and has been previously used to obtain a simple immunological meaning [ 16 , 17 ], its clinical utility warrants future rigorous studies. At the same time, this immune paresis in LT cohorts following vaccination does not mean they lack complete protection, as B-cell negative X-linked Agammaglobulinemia patients have been recently shown to benefit from vaccination due to robust cellular immunity and/or T-cell responses [ 18 ]. How and why such preferential manipulation of immune response occurs is although beyond the scope of the current study; we speculate that there is a possibility of cellular immunity being relatively more resistant than the humoral arm for certain immunosuppressive drugs, as reported for the imidazole-4-carboxamide, 5-(3,3-dimethyl-1-triazeno; DTIC) that is used in the palliation of malignant melanoma [ 19 ].…”

Anti-COVID-19 Vaccination in Patients with Autoimmune-Autoinflammatory Disorders and Primary/Secondary Immunodeficiencies: The Position of the Task Force on Behalf of the Italian Immunological Societies

“…Even patients with PIDs and SIDs do not seem to have contraindications to COVID-19 vaccines. In fact, no higher frequency of AEs was observed in two preliminary studies, the first one on 11 immune deficient patients (10 PIDs and 1 SID) [98] and the other on 26 patients with inborn errors of immunity (26 PIDs) [99], where substantial safety of the mRNA Pfizer vaccine and satisfactory immunogenicity was observed, except for the four patients with X-linked agammaglobulinemia, in whom an adaptive cellular response was observed. A recent study confirmed the lack of antibody response in patients with X-linked agammaglobulinemia, compensated by the induction of an adaptive cellular response, whereas the response of patients with Common Variable Immunodeficiency was found to be unsatisfactory and non-protective at both cellular and humoral levels [100].…”

“…* The risk-benefit evaluation of temporary immunosuppressive treatment interruption should be done by the immunology specialist based on the clinical picture. Regarding PIDs, the presence of Ig replacement therapy does not seem to have interfered with the cellular and humoral immune response observed in most patients, except for patients with X-linked agammaglobulinemia, who did not show antibody response, but were protected by the adaptive cellular immunity[98,99]. However, immunoglobulin for intravenous (IVIg) or subcutaneous (SCIg) use should not be administered in the same time period as vaccination, because it is impossible to check the humoral vaccine response, given that IVIg/SCIg may contain different concentrations of anti-SARS-CoV-2 antibodies[115,116].…”

“…Although in the pre-approval studies details on the possible presence of patients with AIAIDs in the study population have not been provided, recent studies have reported substantial safety and immunogenicity of these vaccines in patients with AIAIDs [48][49][50]92,[106][107][108]. Even in PIDs, two preliminary studies [98,99] have shown the substantial safety and immunogenicity of the mRNA vaccines. Finally, COVID-19 vaccines were safe and immunogenic in onco-hematologic pathologies, and mRNA vaccines were more immunogenic than the adenoviral vaccine [101].…”

SARS-CoV-2 Neutralization in Convalescent Plasma and Commercial Lots of Plasma-derived Immunoglobulin

“…Therefore, the reactivity and neutralizing potency of these IgG pharmaceutical products are directly dependent on the epidemiologic experience of the donor population [19][20][21].…”