Human type I IFN deficiency does not impair B cell response to SARS-CoV-2 mRNA vaccination

Abstract

Inborn and acquired deficits of type I interferon (IFN) immunity predispose to life-threatening COVID-19 pneumonia. We longitudinally profiled the B cell response to mRNA vaccination in SARS-CoV-2 naive patients with inherited TLR7, IRF7, or IFNAR1 deficiency, as well as young patients with autoantibodies neutralizing type I IFNs due to autoimmune polyendocrine syndrome type-1 (APS-1) and older individuals with age-associated autoantibodies to type I IFNs. The receptor-binding domain spike protein (RBD)–specific memory B cell response in all patients was quantitatively and qualitatively similar to healthy donors. Sustained germinal center responses led to accumulation of somatic hypermutations in immunoglobulin heavy chain genes. The amplitude and duration of, and viral neutralization by, RBD-specific IgG serological response were also largely unaffected by TLR7, IRF7, or IFNAR1 deficiencies up to 7 mo after vaccination in all patients. These results suggest that induction of type I IFN is not required for efficient generation of a humoral response against SARS-CoV-2 by mRNA vaccines.

Human inherited complete STAT2 deficiency underlies inflammatory viral diseases

“…Despite the high prevalence of herpesvirus infections in the general population and in STAT2-deficient patients, no life-threatening herpesvirus infections were reported in this cohort, beside one case of fatal HSE. No major anomalies in the immunophenotype or in antibody responses were detected in STAT2-deficient patients, in agreement with recent work evidencing normal antibody response to mRNA SARS-CoV-2 vaccines in the absence of type I IFN signaling (60). An overview of the infectious and immunologic phenotype of patients with AR complete STAT2, IFNAR1, IFNAR2, STAT1, IRF9, IRF7, and IL10RB deficiencies, and patients with autosomal dominant or AR TLR3 deficiency, is presented in Table 3.…”

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

“… 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. 175 …”

Omicron BA.1 breakthrough infection drives long-term remodeling of the memory B cell repertoire in vaccinated individuals

“…These individuals were sampled at three time points (<1, 2 and 6 months) after BA.1 breakthrough infection to fully characterize the B cell response from the early extra-follicular reaction to the late settlement of long-term memory, combining multiparameter flow cytometry analysis, single-cell RNA-sequencing (scRNA-seq) and single cell culture of spike (S) and RBD-specific B cells ( Figure 1A and Figure S1 ). Four of these individuals had been previously sampled after their second and/or third dose of mRNA vaccine ( Table S1) (Sokal et al , 2022, 2023). This provided us with a unique setting to decipher the selection processes occurring at the level of the MBC repertoire upon BA.1 breakthrough infection on a per-individual basis.…”