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This research has not been peer-reviewed. This is a preliminary report that should not be regarded as conclusive, guide clinical practice/health-related behaviour, or be reported in news media as established information.
Background: Immune suppression is a clinical feature of chronic lymphocytic leukaemia (CLL) and patients show increased vulnerability to SARS-CoV-2 infection and suboptimal antibody responses.
Method: We studied antibody responses in 500 patients following dual COVID-19 vaccination to assess the magnitude, correlates of response, stability and functional activity of the spike-specific antibody response with 2 different vaccine platforms.
Results: Spike-specific seroconversion post-vaccine was seen in 67% of patients compared to 100% of age-matched controls. Amongst responders, titres were 3.7 times lower than the control group. Antibody responses showed a 33% fall over the next 4 months. The use of an mRNA (n=204) or adenovirus-based (n=296) vaccine platform did not impact on antibody response. Male gender, BTKi therapy, prophylactic antibiotics use and low serum IgA/IgM were predictive of failure to respond. Antibody responses after CD20-targeted immunotherapy recovered 12 months-post treatment. Post-vaccine sera from CLL patients with Spike-specific antibody response showed markedly reduced neutralisation of the SARS-CoV-2 delta variant compared to healthy controls. Patients with previous natural SARS-CoV-2 infection showed equivalent antibody levels and function as healthy donors after vaccination.
Interpretation: These findings demonstrate impaired antibody responses following dual COVID-19 vaccination in patients with CLL and further define patient risk groups. Furthermore, humoral protection against the globally-dominant delta variant is markedly impaired in CLL patients and indicates the need for further optimisation of immune protection in this patient cohort.