Elevated CD21low B Cell Frequency Is a Marker of Poor Immunity to Pfizer-BioNTech BNT162b2 mRNA Vaccine Against SARS-CoV-2 in Patients with Common Variable Immunodeficiency

Abstract

Purpose Limited 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). Methods In 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. Results A 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. Conclusions CVID 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.

Role of mTOR inhibitor in the cellular and humoral immune response to a booster dose of SARS-CoV-2 mRNA-1273 vaccine in kidney transplant recipients

“…As for cellular response, we did not find a correlation between the different clinical or treatment variants of the patients, although the transplanted cohort showed a lower response rate, both in CD8 and CD4 T cells, compared to control group. These results coincide with those of other studies in cohorts of patients with pharmacological immunosuppression, such as hematological cancer ( 19 ), as well as patients with various types of immunodeficiencies ( 20 , 21 ). These studies also found no correlation between T-cell response and the clinical characteristics of the patients.…”

Impact of SARS-CoV-2 infection and COVID-19 on patients with inborn errors of immunity

“…The general findings from these studies were that (1) fewer patients mounted SARS-CoV-2–specific IgG (30-75%) and T-cell responses (∼50-70%) compared to healthy donors (∼95-100%), (2) titers of SARS-CoV-2–specific IgG, efficacy of virus neutralization, and magnitude of T-cell responses were reduced in patients compared to healthy donors, and (3) poor vaccine-induced immunity in patients correlated with reduced numbers of CD4 + T cells or memory B cells, low serum IgG and IgA, and older age. 80 , 158 , 159 , 160 , 161 , 162 , 163 , 164 , 165 , 166 , 167 , 168 , 169 , 170 , 171 , 172 , 173 Importantly, IEI that disrupt type I IFN–mediated immunity or autoantibodies against type I IFN do not impair humoral immune responses to RNA vaccines. 174 Furthermore, despite normal levels of neutralizing IgG, some patients with anti–type I IFN autoantibodies develop breakthrough COVID-19 pneumonia.…”

Impaired B Cell Recall Memory and Reduced Antibody Avidity but Robust T Cell Response in CVID Patients After COVID-19 Vaccination

“…Previous vaccination studies in CVID patients described the potential impact of the type of vaccine and distribution of B cell subsets affecting vaccination responses [ 46 ]. Regarding COVID-19 vaccine response in CVID, a range of immunological and clinical factors have been described, including non-infectious complications and ongoing immunosuppressive therapy as well as elevated CD21 low B cells, low B cells, low naïve T cells, and reduced IgA and IgM levels [ 7 , 11 , 47 ]. In our cohort, CVID seroresponder and non-seroresponder did not differ in any key immunological parameter; however the small number of patients limits the interpretation.…”