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

Intact B cell responses to SARS-CoV-2 mRNA vaccines in patients with genetic or acquired type I IFN deficiencies suggest that type I IFNs induced by mRNA vaccines are not required for vaccine efficacy. 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.

Automated summary

Intact B cell responses to SARS-CoV-2 mRNA vaccines were observed in patients with genetic or acquired type I IFN deficiencies, indicating that type I IFNs induced by mRNA vaccines are not necessary for vaccine efficacy. This study suggests that the generation of a humoral response against SARS-CoV-2 by mRNA vaccines does not require the induction of type I IFN.