Abstract
PurposeLimited data is available on the effect of COVID-19 vaccination in immunocompromised individuals. Here, we provide the results from vaccinating a single-center cohort of patients with common variable immunodeficiency (CVID).MethodsIn a prospective, open-label clinical trial, 50 patients with CVID and 90 age-matched healthy controls (HC) were analyzed for SARS-CoV-2 spike antibody (Ab) production after one or two doses of the Pfizer-BioNTech BNT162b2 mRNA vaccine. Additionally, in selected patients, SARS-CoV-2 spike-specific T-cells were assessed.ResultsA potent vaccine-induced anti-spike–specific IgG Ab response was observed in all the HC. In contrast, only 68.3% of the CVID patients seroconverted, with median titers of specific Ab being 83-fold lower than in HC. In fact, only 4/46 patients (8.6%) of patients who were seronegative at baseline reached the threshold for an optimal response (250 U/mL). Using the EUROclass definition, patients with either a reduced proportion, but not absolute counts, of switched memory B-cells or having an increased frequency of CD21low B-cells generally generated poor vaccine responses. Overall, CVID-patients had reduced spike-specific IFN-γ positive CD4+ T cell responses 2 weeks after the second dose, compared to HC. The total CD4 and CD4 central memory cell counts correlated with humoral immunity to the vaccine.ConclusionsCVID patients with low frequency of switched memory B-cells or an increased frequency of CD21low B-cells according to the EUROclass definition demonstrated poor responses to Pfizer-BioNTech BNT162b2 mRNA vaccination. Cellular immune responses were significantly affected, affirming that the defect in CVID is not limited to humoral immunity.
Highlights
Common variable immunodeficiency disorders (CVID) form a heterogeneous group of immunodeficiencies likely encompassing several different etiologies [1]
As pointed out in the International Consensus Document (ICON) on CVID, there is considerable knowledge regarding the immunological response to a few vaccines, for most of them, information is scarce or lacking [3]
The patients with CVID studied here represent a subset of an ongoing prospective, open-label clinical trial where 449 immunocompromised patients and 90 controls were vaccinated with two doses of the Pfizer-BioNTech BNT162b2 mRNA vaccine [11] and evaluated at day 35 (2 weeks after dose 2), as specified in the original safety and immunogenicity study [19]
Summary
Common variable immunodeficiency disorders (CVID) form a heterogeneous group of immunodeficiencies likely encompassing several different etiologies [1]. As pointed out in the International Consensus Document (ICON) on CVID, there is considerable knowledge regarding the immunological response to a few vaccines, for most of them, information is scarce or lacking [3] To this end, a rather unique feature of CVID is that vaccination is part of the diagnostic strategy. The majority of patients with CVID respond poorly to pure polysaccharide-vaccines but may mount weak responses to protein and conjugate vaccines [4]. While such vaccinations serve two purposes, diagnostic and prophylactic, the response may be difficult to interpret due to previous exposure to these bacteria in the past as well as previous vaccinations
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