Thus, SARS-CoV-2 vaccination in the context of a partially compromised immune system may favor reactivation of pre-existing memory over the stimulation of naïve B cells, similar to what has been observed for responses to influenza following vaccination in the elderly.43 Given the essential contributions of naïve B and CD4+ T cells to de novo responses, their decline over the CLL disease course is expected to worsen the capacity for engaging neoantigens. Here, CD4 is linked to B-cell chronic lymphocytic leukemia.