B cell chronic lymphocytic leukemia (CLL) is the most common subtype of adult leukemia and is associated with profound secondary immunodeficiency. SARS-CoV-2 infection has been a significant cause of morbidity and mortality (Mato et al., 2020; Pagano et al., 2021), and immunological responses against SARS-CoV-2 vaccines are impaired (Fendler et al., 2021) in patients with CLL. In particular, reduced 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). However, questions regarding optimal immune protection remain unresolved, and these include the potential for additional vaccine doses to increase seroconversion rate, potential humoral and cellular immune protection against Omicron, and the impact of vaccine delivery on breakthrough infection rate and clinical outcome.

We determined antibody and cellular immune responses after third and fourth vaccine dose in participants in the CLLVR study 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%) had received the BNT162b2 vaccine (Pfizer/BioNTech) as primary series and 243 (60%) had received the ChAdOx1 vaccine (Oxford/AstraZeneca). Almost all