Objective:

To assess humoral and cell-mediated immune responses and 12-month safety after adjuvanted RSVPreF3 vaccination in lung and allogeneic hematopoietic cell transplant recipients.

Approach:

• Design and participants: Nonrandomized clinical trial at one center involving 86 adults: 40 lung transplant recipients and 46 allogeneic hematopoietic cell transplant recipients. Each received one vaccine dose.
• Assessments: Neutralizing antibodies, anti-RSVPreF IgG, and polyfunctional T cells were assessed before vaccination and at 1, 6, and 12 months. Safety was followed for 12 months.

Key Findings:

• Neutralizing antibody titers rose after vaccination, remained stable through 6 months, and declined by 12 months. At 12 months, seroconversion was observed in 24% of lung transplant and 17% of allogeneic HCT recipients.
• Binding antibody concentrations increased after vaccination and remained above baseline at 12 months; levels were higher in lung transplant recipients.
• Polyfunctional CD4+ T-cell frequencies increased and remained significantly above baseline at 12 months in both groups. RSV-specific polyfunctional CD8+ T-cell responses were largely undetectable.
• No vaccine-related rejection or graft-vs-host disease events were reported. Thirty-two hospitalizations occurred during follow-up, none attributed to vaccination.

Interpretation:

The authors report that vaccination was immunogenic and well tolerated over 12 months. Antibody responses were consistently higher in lung transplant recipients, while CD4+ T-cell responses were comparable between groups. Immune correlates of protection against RSV remain undefined.

Limitations:

• Single-center study with a modest sample size and no nontransplant control group.
• No comparison with other licensed RSV vaccines; alloHCT recipients receiving systemic immunosuppression for graft-vs-host disease were excluded.
• Neutralization testing included RSV-A only.
• Variable enrollment timing meant participants could have different exposure opportunities across RSV seasons.

Conclusion:

Over 12 months, adjuvanted RSVPreF3 vaccination was associated with increased antibody and polyfunctional CD4+ T-cell responses in lung and allogeneic hematopoietic cell transplant recipients. Neutralizing antibody titers declined by 12 months, while binding antibodies and CD4+ T-cell responses remained above baseline. The authors note that immune correlates of protection remain undefined.