Reactogenicity and Immunogenicity of RSV Vaccines in Immunocompromised Individuals With Hematological Malignancies

ABSTRACT Background Adults with hematologic malignancy (HM) are at increased risk for severe respiratory syncytial virus (RSV) infection. Immunogenicity and durability data of prefusion F ‐based RSV vaccines in HM remain limited. Methods In a prospective cohort, adults with HM and healthy controls (HCs) received one RSV vaccine (adjuvanted RSVPreF3 or non‐adjuvated RSVpreF). Serum was collected pre‐vaccination and at 1, 3, and 6‐months for anti‐fusion glycoprotein (FGP) IgG to RSV A/B; 7‐day reactogenicity was assessed. A subset ( n = 13) underwent T‐cell analyses for RSV F‐specific CD4 + and CD8 + T‐cell responses. Results Fifty‐five HM participants and 16 HCs were enrolled; 60% had prior hematopoietic cell transplantation. Mild reactogenicity occurred in ∼25%, with no severe events reported. Anti‐FGP titers were higher in HCs than HM at all visits (all p < 0.01); RSV‐A median titers were 0.153 versus 0.055 Normalized average enzymes per bead (nAEB) at baseline and 1.154 versus 0.113 (nAEB) at 1 month (HC vs. HM). Within HM, anti‐FGP increased at 1 month for RSV A and B but waned thereafter; RSV‐A remained above baseline at 3 months only, and RSV‐B was not sustained beyond 1 month. Baseline‐to‐1‐month fold changes were similar between HM and HCs. RSV F‐specific CD4 + and CD8 + T cells increased at 1 month ( p = 0.027; p = 0.031), with CD8 + responses also increased at 3 months ( p = 0.006). One RSV infection occurred 5 days post‐vaccination. Conclusions RSV vaccination was well tolerated and induced early humoral and cellular responses in HM, but antibody magnitude and durability were reduced compared with HCs, supporting the need to optimize vaccination strategies for HM populations.