The response to BTN62b2 booster doses demonstrates that serum antibodies do not predict the establishment of immune B-cell memory in common variable immune deficiencies

In patients with common variable immune deficiencies, primary vaccination followed by two booster doses is recommended for protection against COVID-19. Seroconversion has been shown in 60% of patients. We have no information on whether serum antibodies reflect the generation of durable immune memory. In a longitudinal study on 47 common variable immune deficiencies patients who received the third and fourth vaccine dose, we show that the measurement of specific antibodies is not sufficient to predict the establishment of immune memory and the ability to respond to antigen re-exposure. Our results indicate that the combination of antibodies and memory B cells responses represents a more reliable read-out of vaccine immune efficacy in vulnerable patients. This analysis may not only identify individuals remaining unprotected after vaccination and unable to respond to additional booster doses, but also address the search for the underlying immune defect and suggest patient-tailored management strategies. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The study was supported by funding of the Italian Ministry of Health COVID2020-12371817 and by Grant 5 per mille, 2021. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the Ethical Committee of the Sapienza University of Rome (Prot. 0521/2020, July 13, 2020) and performed in accordance with the Good Clinical Practice guidelines, the International Conference on Harmonization guidelines, and the most recent version of the Declaration of Helsinki I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Resource Availability. Lead Contact Further information and requests for resources and reagents should be directed to and will be fulfilled by the lead contact, Rita Carsetti (rita.carsetti{at}opbg.net) Materials Availability All reagents will be made available on request after completion of a Materials Transfer Agreement.