Response to Dr Belviranli Keskin's Comments

To the editor—We appreciate Dr Belviranli Keskin's interest in our work and thank her for her comments. We respond to each of her points below. SARS-CoV-2 response dynamics and the possibility of missing a “kinetic window” of the immune response. Dr Belviranli Keskin questions the differences in timing for the analysis of SARS-CoV-2 B cell responses between solid organ transplant recipients (SOTR) and controls in our paper [1], and she references the limited “kinetic window” when circulating plasmablasts emerge during early immune responses. The goal of measuring SARS-CoV-2 responses in our study was to define individual SOTR as vaccine responders or nonresponders, not to compare the magnitude or characteristics of the peak immune response in SOTR to controls. Since humoral responses are known to be significantly delayed in SOTR compared to healthy individuals [2–4], we chose later postvaccine sampling time points to enhance the likelihood of detecting any response in SOTR. For SOTR individuals showing an earlier-peaking immune response (ie, similar to healthy controls), this would remain detectable within our sampling window since SARS-CoV-2 mRNA vaccine-elicited responses are readily detectable for many weeks beyond the peak [5]. Of note, these cellular responses are detected not by the analysis of plasmablasts or activated B cell populations, but by the analysis of circulating B cells that bound to the receptor binding domain within the SARS-CoV-2 spike protein, using similar methods to our earlier work cited by Dr Belviranli Keskin [5]. We also performed serologic analysis to robustly confirm each individual's response status, since antibody titers wane more slowly than activated cell populations. Finally, we would like to highlight that the vaccine response measure played no role in our B cell-based subject group classification, which was based upon frequencies of basic B cell populations in the blood. Memory versus naive B cell subset frequencies (as opposed to antigen-specific B cell populations) are large and do not fluctuate appreciably after vaccination. As such, our classification results would remain consistent regardless of sample timing.