Background In mid-December 2020, Israel had started a nationwide mass vaccination campaign against COVID-19. In the first few weeks, medical personnel, elderly citizens and patients with chronic diseases were prioritized. As such, patients with primary and secondary immunodeficiencies were encouraged to receive the vaccine. While the efficacy of RNA-based COVID-19 vaccines was demonstrated in the general population, little is known about their efficacy and safety in patients with Inborn Errors of Immunity (IEI). Objectives To evaluate the humoral and cellular immune response to COVID-19 vaccine in a cohort of IEI patients. Methods 26 adult patients were enrolled, and plasma and peripheral blood mononuclear cells were collected two weeks following the second dose of Pfizer-BioNTech COVID-19 vaccine. Humoral response was evaluated by testing anti-SARS-CoV-2 Spike (S) Receptor Binding Domain (RBD) and anti-Nuclear (N) antibody titers, and evaluation of neutralizing ability by inhibition of RBD:ACE2 binding. Cellular immune response was evaluated by ELISpot, estimating IL2 and IFNγ secretion in response to pooled SARS-CoV-2 S or M peptides. Results Our cohort included 18 patients with predominantly antibody deficiency, 2 with combined immunodeficiency, 3 with immune-dysregulation, and 3 with other genetically defined diagnoses. 22/26 were receiving immunoglobulin replacement therapy. 18/26 developed specific antibody response and 19/26 showed S-peptide specific T-cell response. None of the patients reported significant adverse events. Conclusion Vaccinating IEI patients is safe, and most patients were able to develop vaccine specific antibody response, S-protein specific cellular response or both.

Data are scarce regarding both safety and immunogenicity of the BNT162b2 mRNA COVID-19 vaccine in patients undergoing immune cell therapy, thus we prospectively evaluated these 2 domains in patients receiving this vaccine after allogeneic HCT (n=66) or after CD19-based CART therapy (n=14). Overall, vaccine was well tolerated, with mild non-hematologic vaccine-reported adverse events in minority of the patients. 12% (after first dose) and 10% (after second dose) of the patients developed cytopenia and there were 3 cases GVHD exacerbation after each dose. A single case of impending graft rejection was summarized as possibly related. Evaluation of immunogenicity showed that 57% of patients after CART infusion and 75% patients after allogeneic HCT had evidence of humoral and/or cellular response to the vaccine. On cox regression model, longer time from infusion of cells, female sex, and higher CD19 + cells were associated with a positive humoral response, whereas higher CD4 + /CD8 + ratiowas correlated with a positive cellular response, confirmed by ELISpot test. We conclude that BNT162b2 mRNA COVID-19 vaccine has impressive immunogenicity in patients after allogeneic HCT or CART. Adverse events were mostly mild and transient, but some significant hematologic events were observed, hence, patients should be closely monitored.

Background Little is known about vaccine efficacy and sustainability among people with HIV (PWH). We estimated humoral and cellular immune responses post-vaccination with BNT162b2 mRNA COVID-19 vaccine among PWH in Tel-Aviv medical center. Methods The vaccine humoral response was evaluated by measuring IgG titers of anti-spike receptor-binding domain antibodies (anti-RBD IgG). Cellular response was assessed by stimulating donor peripheral blood mononuclear cells with pooled complete S-peptide mix. Results 136 PWH who completed 2 doses of the SARS-CoV-2 vaccine were tested for anti-RBD IgG and compared with 61 vaccinated healthcare workers (HCW). The antibody titers were similar between the groups (median of 118 BAU/ml for PWH and 101.4 BAU/ml for HCW, p=0.231), although the mean time from 2 nd vaccine was 4.5 months in PWH and 6.7 months in HCW (P<0.0001). Longer time from 2 nd vaccine dose was associated with decreased antibody level, as were CD4 counts of <300 cells/µL compared with higher CD4 counts (25.1 BAU/ml vs. 119.3 BAU/ml, respectively, p=0.047). There was no difference in cellular immune response between vaccinated PWH, convalescent unvaccinated PWH and vaccinated HCW. Conclusions The humoral immune response of PWH was comparable to those of HCW after BNT162b2 mRNA vaccination. Cellular immune response did not differ between vaccinated PWH, convalescent PWH and vaccinated HCW. PWH with CD4 count of < 300 cells/µL (n=9) had lower antibody titers compared with patients with counts of >300 cells/µL (n=127).