Safety and immunogenicity of adjuvanted respiratory syncytial virus vaccine in high-risk transplant recipients: An Interventional Cohort Study.

Objectives: Allogeneic hematopoietic cell transplant (alloHCT) and lung transplant (LT) recipients are at highest risk for severe respiratory syncytial virus (RSV) disease, even as compared to other immunocompromised groups. Notably, these groups were excluded from published RSV vaccine clinical trials. The aim of this study was to determine the safety and immunogenicity of adjuvanted RSVPreF3 vaccine in adult alloHCT and LT recipients.

Methods: Adult alloHCT (≥6 months post-transplant) and LT (≥3 months post-transplant) recipients were enrolled and administered a single dose of adjuvanted RSVPreF3 vaccine. Blood samples were collected at baseline and 4-6 weeks post-immunization to assess neutralizing antibodies (NAb), anti-RSVPreF-IgG antibody levels and RSV-specific polyfunctional T-cells. Safety was assessed through participant-led diaries and follow-up.

Results: 86 participants (46 alloHCT, 40 LT) were enrolled, with median follow-up of 191 days [interquartile range (IQR) 170-248]. Median age was 59 years (IQR 45.5-67.3) for LT and 64 years (IQR 59-69) for alloHCT recipients. NAb titres increased post-vaccination in both groups (alloHCT: 1.3-fold, LT: 3.0-fold; p<0.0001). Seroconversion by NAb occurred in 15/45 (33.3%) alloHCT and 19/39 (48.7%) LT recipients. IgG binding antibody levels increased significantly in both groups (3.3-fold in LT, p=0.0018; 2.3-fold in alloHCT, p=0.0015). CD4⁺ polyfunctional T-cell responses were detected in 30/42 (71.4%) alloHCT and 28/35 (80.0%) LT recipients post-vaccination. CD8⁺ T-cell responses were lower, but frequencies increased in LT recipients after vaccination (p=0.024). Overall, the vaccine was well tolerated with Grade 1 pain the most reported adverse event (54/86, 62.8%). There was no study intervention-related withdrawal. Three LT recipients developed RSV infection post vaccination; two required hospitalization.

Conclusions: The adjuvanted RSVPreF3 vaccine was immunogenic and well-tolerated with modest seroconversion but robust CD4⁺ T-cell responses. These data support the benefit of RSV vaccination but underscore the need for further strategies to optimize NAb and CD8⁺ T-cell responses in this high-risk population.