Safety and immunogenicity of adjuvanted respiratory syncytial virus vaccine in high-risk transplant recipients: an interventional cohort study

Abstract

Objectives: Allogeneic haematopoietic 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 posttransplant) and LT (≥3 months posttransplant) recipients were enrolled and administered a single dose of adjuvanted RSVPreF3 vaccine. Blood samples were collected at baseline and 4-6 weeks postimmunization 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: Eighty-six participants (46 alloHCT, 40 LT) were enrolled, with median follow-up of 191 days (interquartile range [IQR] 170-248). The median age was 59 years (IQR 45.5-67.3) for LT and 64 years (IQR 59-69) for alloHCT recipients. NAb titres increased postvaccination in both groups (alloHCT: 1.3-fold, LT: 3.0-fold; p < 0.0001). Seroconversion by NAb occurred in 15 of 45 (33.3%) alloHCT and 19 of 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 of 42 (71.4%) alloHCT and 28/35 (80.0%) LT recipients postvaccination. 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 postvaccination; 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.

Keywords: Haematopoietic cell transplantation; Immunocompromise; Lung transplantation; Respiratory syncytial virus; Vaccination.