Immunogenicity and clinical outcomes of booster mRNA vaccine BNT162b2 in primary antibody deficiencies

Purpose:Anti-SARS-CoV-2 mRNA vaccines may elicit humoral responses in patients with primary antibody deficiency. However, this response is limited by its rapid waning and low levels of virus-neutralizing antibodies. There is limited evidence for the efficacy of the booster vaccination in patients with primary antibody deficiencies. Methods:This prospective observational cohort study focused on the clinical outcomes (proportion of infected patients, disease severity, and adverse event incidence) and dynamics of humoral immune responses (specific post-vaccination and virus-neutralizing antibodies) after booster (third) mRNA anti-SARS-CoV-2 vaccine in patients with common variable immunodeficiency (CVID). The patients were followed-up for seven months. Results:Eighteen participants were enrolled from 21 screened patients with CVID. One month after the booster vaccination, the proportion of responders increased from 16.7%, and the mean concentration of anti-SARS-CoV-2 RBD antibodies increased from 13.95 U/mL to 72.2% and 302.6 U/mL, which was significantly lower compared to healthy donors (mean 1949 U/ml). Patients with CVID also had reduced titers of virus-neutralizing antibodies. Notably, response rate and mean specific antibody concentrations increased within the follow-up period up to 100% and 1346 U/mL, respectively, at month seven. These results may be confounded by the passivetransmission of specific antibodies. Local reactions were the most common adverse events. No severe adverse events were reported. Conclusion:Booster vaccination and passively transmitted anti-SARS-CoV-2 specific antibodies from immunoglobulin replacement therapy result in high serum levels of specific antibodies. However, this is limited by lower titers of neutralizing antibodies and different immunogenicity against viral variants. Administration of a booster dose of the BNT162b2 vaccine was safe; no new safety concerns were raised.