Impact of two and three dose COVID-19 vaccination schedule on transcriptional, humoral and T cell immune response in previously heavily treated, single agent treated and naïve CLL patients

This study investigates the innate immune response to COVID-19 mRNA and vector-based vaccines in 15 patients with chronic lymphocytic leukemia (CLL). It assessed the innate and adaptive immune response of CLL patients after booster vaccination and generated a comprehensive transcriptome (mRNA-seq) analysis of peripheral blood mononuclear cells (PBMCs). Specifically, this investigation on a '3-dose' cohort of heavily pretreated CLL patients, who had tested seronegative following a two-dose homologous vaccination (either BNT162b2 or ChAdOx1) and had received a third heterologous dose. A '2-dose' cohort encompassed treatment-naïve or minimal pretreated CLL patients, who showed a serological immune response after the first vaccination and had received a second dose. Bulk mRNA-seq was conducted on PBMCs harvested prior to the vaccination and at days 2 and 7 post vaccination. The innate immune response observed in all patients was independent of the IgG antibody response. Expression of interferon-regulated genetic pathways was induced within two days after vaccination. Overall design: RNA-seq were performed with peripheral blood mononuclear cells (PBMCs) from chronic lymphocytic leukemia (CLL) patients who had received the BNT162b2 or ChAdOx1 vaccine.