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Here we comprehensively examined humoral and cellular responses to vaccine in CLL patients. Seroconversion was observed in 55.2% of CLL with lower rate and antibody titres in treated patients. T\u2010cell responses were detected in a significant fraction of patients. CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> frequencies were significantly increased independent of serology with higher levels of CD4<jats:sup>+<\/jats:sup> cells in patients under a Bruton tyrosine kinase (BTK) or a B\u2010cell lymphoma 2 (BCL\u20102) inhibitor. Vaccination skewed CD8<jats:sup>+<\/jats:sup> cells towards a highly cytotoxic phenotype, more pronounced in seroconverted patients. A high proportion of patients showed spike\u2010specific CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> cells producing interferon gamma (IFN\u03b3) and tumour necrosis factor alpha (TNF\u03b1). Patients under a BTK inhibitor showed increased production of IFN\u03b3 and TNF\u03b1 by CD4<jats:sup>+<\/jats:sup> cells. Vaccination induced a Th1 polarization reverting the Th2 CLL T\u2010cell profile in the majority of patients with lower IL\u20104 production in untreated and BTK\u2010inhibitor\u2010treated patients. Such robust T\u2010cell responses may have contributed to remarkable protection against hospitalization and death in a cohort of 540 patients. Combining T\u2010cell metrics with seroprevalence may yield a more accurate measure of population immunity in CLL, providing consequential insights for public health.<\/jats:p>","DOI":"10.1111\/bjh.18602","type":"journal-article","created":{"date-parts":[[2022,12,9]],"date-time":"2022-12-09T09:25:51Z","timestamp":1670577951000},"page":"45-57","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Immune correlates of protection by vaccine against <scp>SARS\u2010CoV<\/scp>\u20102 in patients with chronic lymphocytic leukaemia"],"prefix":"10.1111","volume":"201","author":[{"given":"Daniele","family":"Sorcini","sequence":"first","affiliation":[{"name":"Department of Medicine and Surgery, Institute of Hematology, Centro di Ricerca Emato\u2010Oncologica (CREO) University of Perugia  Perugia 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