In particular, decreased rates of seroconversion and antibody titer have been reported (Parry et?al

In particular, decreased rates of seroconversion and antibody titer have been reported (Parry et?al., 2021; Greenberger et?al., 2021; Herishanu et al., 2022) and associate with reduced serum immunoglobulin level or use of medication such as Bruton tyrosine kinase inhibitors or anti-CD20 antibodies (Parry et?al., 2021; Herishanu et al., 2022). together with age-matched healthy donor controls (n?= 93). Blood samples were taken from 404 patients at a median time of 20 days following the third dose. Of those patients, 161 (40%) experienced received the BNT162b2 vaccine (Pfizer/BioNTech) as main series and 243 (60%) experienced received the ChAdOx1 vaccine (Oxford/AstraZeneca). Almost all patients (393/404) Tolnaftate received an mRNA vaccine for their third dose (375 received BNT162b2 and 18 received mRNA-1273). Samples were also collected from 186 patients following the fourth vaccine dose (Table S1). Patients with clinical or serological evidence of prior natural SARS-CoV-2 contamination were excluded from analysis. Spike-specific antibody responses have previously been reported to develop in 66% (322/486) of patients within the CLL-VR study following the first two vaccine doses compared to 100% of controls (Parry et?al., 2021). This response rate improved to 80% following the third vaccine dose (298/374) (p 0.0001) (Physique S1A). Analysis of vaccine subtype received during the first two doses showed no difference in seroconversion rate following a heterologous or homologous third dose (ChAdOx1/mRNA response rate 81% [187/230] vs. BNT162b2/mRNA response rate 77% [111/144], p?= 0.28). However, Tolnaftate the seroconversion rate was not increased further after a fourth vaccine (77%; 132/171), and this indicates that this proportion of patients who develop a spike-specific antibody response following COVID-19 vaccination plateaus after the third vaccine (Physique?S1A). Three seronegative patients became available for study following Tolnaftate breakthrough infections, and natural contamination also failed to generate spike-specific antibodies; this indicates that patients in the seronegative subgroup are broadly refractory to seroconversion. Regardless of vaccine dose number, a low serum IgM, current BTKi therapy, or imminent planned treatment were impartial predictors of poor response with?an 81% (p?= 0.003), 90% (p?= 0.021), and 96% (p = 0.027) reduction in odds?of?response respectively after the fourth dose. In those patients who experienced a positive antibody response following vaccination, titers increased by 4.5-fold after the third vaccine dose (Geometric mean [GM] 404 arbitrary models [AU]/ml [95% confidence interval (CI) 311C526] vs. 1,820 AU/ml [95% CI 1,340C2,480], p 0.0001) and became comparable to values seen within healthy controls following main series dual vaccination (GM 2,317 [95% CI 1,191C4,508] AU/ml) (Physique?S1B). No difference in antibody titer was observed following heterologous or homologous vaccination (ChAdOx1/mRNA GM 2,580 [95% CI 1,150C,5780] vs BNT162b2/mRNA 1,830 [95% CI 526C6,340], p?= 0.72). Cellular responses were initially assessed through the use of IFN-QuantiFERON after the second (n?= 19) and third vaccine dose (n?= 70). These responses were strong and comparable with values seen in control donors after Mouse monoclonal to IL-16 two vaccine doses (CLL for two doses, 0.25 [interquartile range (IQR) 0.08C0.46] IU/mL and for three doses, 0.15 [IQR 0.03C0.3] IU/mL vs. controls for two doses, 0.14 [IQR 0.06C0.36] IU/mL) (Figure?S1C). Response was found to be markedly higher after the third dose in patients who experienced a heterologous vaccine course (ChAdOx1/mRNA 0.22 [IQR 0.06C0.55] Tolnaftate IU/mL vs mRNA/mRNA 0.04 [IQR 0.02C0.25] IU/mL; p?= 0.009). We next assessed the quality of humoral and cellular vaccine-induced immunity against the Omicron variant that has become globally dominant since its initial description in November 2021. Neutralizing antibody titers after the third vaccine dose were markedly reduced against Omicron compared to the ancestral Tolnaftate variant, but they were equivalent in patients and controls (ancestral, CLL GM 1,780 [95% CI 969C3,280] U/ml vs controls 2,600 [95% CI 1,423C4,738] U/ml; Omicron, CLL 122.