Patients with B-cell malignancies experience reduced antibody responses with class switching defect following BNT162b2 SARS-CoV-2 vaccination

Vaccines having aided in escaping the majority of the population from immunological naïvety, our strategies are now shifting towards an increased focus on identifying and protecting the extremely vulnerable. We here describe the results of testing 12 patients, those with lymphoid malignancies having been targeted their B-cells for therapy with rituximab-containing regimens or a Bruton tyrosine kinase inhibitor, for anti-SARS-CoV-2 spike antibodies after receiving the BNT162b2 mRNA vaccine doses. The interval from last dosing of B-cell depletion therapy to SARS-CoV-2 vaccination was at median 5.3 (range 3.1–6.6) months. Using the ‘seroprotection’ threshold of 775 [BAU/mL] for the anti-spike antibody titer, our finding points out the crucial unresponsiveness of the targeted population with 0/12 (0%) achieving ‘seroprotection’. Although IgG seroconversion was observed in 4/12 (33%), supporting the overall benefit of vaccination, the figures still point out a potential need for optimization of practice. IgA was further less responsive (unsuccessful ‘seroconversion’ in 11/12 (92%)), implicating an underlying class switch defect. Those with depletion on B-cells are caught at a dilemma between, being too early and too late on receiving SARS-CoV-2 vaccines. They wish to get over their immunological naïvety at the earliest, while, in order to assure quality immune memory, are also required to hold the patience for their B-cells to repopulate. Although it remains an issue whether intensified vaccine schedules and/or regimens will lead to stronger immunogenicity or more effective boosters for non-responders, we shall take advantage of every increasing evidence in order to optimize current options.