Abstract
In the face of evolving SARS-CoV-2 variants, immunocompromised patients, particularly those with solid cancers, pose unique challenges in vaccine responsiveness. We investigated the humoral immune responses in solid cancer patients (n=64) undergoing anti-cancer treatments, comparing them to healthcare workers (n=23). Over 12 months, we tracked SARS-CoV-2 spike (S) and receptor binding domain (RBD) specific antibodies, memory B cells, and circulating follicular helper T cells (cTfh) post two to five doses of monovalent or bivalent vaccinations and after Omicron variant breakthrough infections (BTI). After the third vaccination, solid cancer patients exhibited antibody levels against wild-type and variants similar to healthy controls. Notably, post-BTI, these patients showed heightened and sustained antibody responses, indicating the efficacy of hybrid immunity. S-specific memory B cells initially mirrored healthy individuals after the third dose but declined faster. The fourth dose had minimal impact, while the fifth significantly boosted classical memory B cells. Post-BTI, durable S-specific memory B cells increased, irrespective of prior vaccination doses. Our findings highlight the resilient and prolonged humoral immunity induced by repeated vaccinations and BTIs in solid cancer patients, offering critical insights for tailored vaccination strategies in immunocompromised populations.
