SARS-CoV-2 vaccination in rituximab-treated patients: B cells promote humoral immune responses in the presence of T-cell-mediated immunity

Abstract

ObjectivesEvidence suggests that B cell-depleting therapy with rituximab (RTX) affects humoral immune response after vaccination. It remains unclear whether RTX-treated patients can develop a humoral and T-cell-mediated immune response against SARS-CoV-2 after immunisation.MethodsPatients under RTX treatment (n=74) were vaccinated twice with either mRNA-1273 or BNT162b2. Antibodies were quantified using the Elecsys Anti-SARS-CoV-2 S immunoassay against the receptor-binding domain (RBD) of the spike protein and neutralisation tests. SARS-CoV-2-specific T-cell responses were quantified by IFN-γ enzyme-linked immunosorbent spot assays. Prepandemic healthy individuals (n=5), as well as healthy individuals (n=10) vaccinated with BNT162b2, served as controls.ResultsAll healthy controls developed antibodies against the SARS-CoV-2 RBD of the spike protein, but only 39% of the patients under RTX treatment seroconverted. Antibodies against SARS-CoV-2 RBD significantly correlated with neutralising antibodies (τ=0.74, p<0.001). Patients without detectable CD19+ peripheral B cells (n=36) did not develop specific antibodies, except for one patient. Circulating B cells correlated with the levels of antibodies (τ=0.4, p<0.001). However, even patients with a low number of B cells (<1%) mounted detectable SARS-CoV-2-specific antibody responses. SARS-CoV-2-specific T cells were detected in 58% of the patients, independent of a humoral immune response.ConclusionsThe data suggest that vaccination can induce SARS-CoV-2-specific antibodies in RTX-treated patients, once peripheral B cells at least partially repopulate. Moreover, SARS-CoV-2-specific T cells that evolved in more than half of the vaccinated patients may exert protective effects independent of humoral immune responses.

Additional heterologous versus homologous booster vaccination in immunosuppressed patients without SARS-CoV-2 antibody seroconversion after primary mRNA vaccination: a randomized controlled trial

“…In contrast, none of the patients in our study had detectable anti-SARS-CoV-2 antibodies at baseline. Detectable peripheral B-cells serve as a key factor for seroconversion in rituximabtreated patients 14 and randomization was therefore stratified by presence or absence of peripheral B-cells. As described after conventional vaccination with two mRNA vaccine doses, presence of detectable peripheral B-cells was the strongest determinant for seroconversion also in patients receiving an additional booster vaccination.…”

“…Data were calculated as spot-forming cells (SFCs) per 10 6 PBMCs after subtracting of the spots from the negative control (mean spot numbers from three to four unstimulated wells). T-cell responses were considered positive if spot counts were greater than the mean SFCs plus three times the standard deviation from pre-pandemic controls, as defined previously 14 .…”

“…Post hoc exploratory analyses were performed to evaluate factors associated with seroconversion rates by univariate logistic regression analyses. Variable selection was based on previous data in rituximab patients, and included age, concomitant medication, type of booster vaccination and presence or absence of detectable peripheral B-cells 14 . GraphPad Prism (version 9.1.0) was used for the graphical presentation of the data.…”

“…This combination poses a dilemma and therefore a highly unmet clinical need for this group of patients. Those lacking B lymphocytes in the periphery at the time of vaccination and thus did not yet start reconstituting their B-cell pool often fail to seroconvert 14,15 . Although B-cell depleted patients can develop a T-cell response, to date, it is unclear to what extent cellular and humoral responses contribute to protection against SARS-CoV-2 infection.…”

Hybrid immunity versus vaccine-induced immunity against SARS CoV2 in Patients with Autoimmune Rheumatic Diseases

“…Most immunosuppressive drugs appear to have moderate to no effect on immunogenicity. However, drugs like Rituximab have also been shown to be associated with lower rate of seroconversion post-vaccination[15]. We have previously shown that patients on immunosuppressive therapy respond similarly to the healthy controls following SARS-CoV-2 infection[16].…”