Background Data on immune responses to SARS-CoV-2 in patients with Primary Antibody Deficiencies (PAD) are limited to infected patients and to heterogeneous cohorts after immunization. Methods Forty-one patients with Common Variable Immune Deficiencies (CVID), six patients with X-linked Agammaglobulinemia (XLA), and 28 healthy age-matched controls (HD) were analyzed for anti-Spike and anti-receptor binding domain (RBD) antibody production, generation of Spike-specific memory B-cells, and Spike-specific T-cells before vaccination and one week after the second dose of BNT162b2 vaccine. Results The vaccine induced Spike-specific IgG and IgA antibody responses in all HD and in 20% of SARS-CoV-2 naive CVID patients. Anti-Spike IgG were detectable before vaccination in 4 out 7 CVID previously infected with SARS-CoV-2 and were boosted in six out of seven patients by the subsequent immunization raising higher levels than patients naïve to infection. While HD generated Spike-specific memory B-cells, and RBD-specific B-cells, CVID generated Spike-specific atypical B-cells, while RBD-specific B-cells were undetectable in all patients, indicating the incapability to generate this new specificity. Specific T-cell responses were evident in all HD and defective in 30% of CVID. All but one patient with XLA responded by specific T-cell only. Conclusion In PAD patients, early atypical immune responses after BNT162b2 immunization occurred, possibly by extra-follicular or incomplete germinal center reactions. If these responses to vaccination might result in a partial protection from infection or reinfection is now unknown. Our data suggests that SARS-CoV-2 infection more effectively primes the immune response than the immunization alone, possibly suggesting the need for a third vaccine dose for patients not previously infected. Supplementary Information The online version contains supplementary material available at 10.1007/s10875-021-01133-0.
【저자키워드】 COVID-19, SARS-CoV-2, BNT162b2 vaccine, Spike protein, X-linked agammaglobulinemia, Primary antibody deficiencies, Common variable immune deficiencies, Memory cells, Receptor-binding-domain, 【초록키워드】 IgG, Vaccine, BNT162b2 vaccine, immune response, vaccination, SARS-COV-2 infection, Antibody Response, T-cell Response, T-cells, Infection, immunization, memory, vaccine dose, BNT162b2, specificity, Reinfection, Cohort, anti-Spike IgG, RBD, IgA, immune responses, response, Patient, Germinal center, T-cell, CVID, patients, agammaglobulinemia, Anti-spike, B-cell, X-linked agammaglobulinemia, Atypical, B-cells, antibody production, XLA, Reactions, supplementary material, infected patients, second dose, one patient, naïve, heterogeneous, binding domain, Specific, while, spike-specific IgG, variable, common, X-linked, Seven, Result, analyzed, occurred, healthy, subsequent, detectable, generate, infected patient, age-matched control, infected with SARS-CoV-2, of BNT162b2, raising, undetectable, 【제목키워드】 response, induced,