# 224. Immunosuppression and RSV Prefusion F Protein Vaccine Effectiveness in Older Adults: A Prespecified Subanalysis from the DAN-RSV Trial

## TL;DR

This study found that an RSV prefusion F protein vaccine reduced hospitalizations for RSV-related diseases in older adults, including those with weakened immune systems.

## Contribution

The study provides evidence that the RSVpreF vaccine is effective in reducing hospitalizations in immunosuppressed older adults.

## Key findings

- RSVpreF reduced RSV-related hospitalizations in immunosuppressed individuals by 60.5%.
- The vaccine showed consistent effectiveness across both immunosuppressed and non-immunosuppressed groups.
- Hospitalization rates for RSV-related disease were over nine times higher in unvaccinated immunosuppressed individuals.

## Abstract

Immunosuppressed (IS) individuals are at high risk of severe respiratory syncytial virus (RSV) complications. This prespecified analysis of DAN-RSV evaluated the effectiveness of a bivalent RSV prefusion F protein-based vaccine (RSVpreF) in preventing RSV-related and all-cause cardio-respiratory hospitalizations among individuals with and without IS.Table 1.Baseline characteristics according to immunosuppression status.Values are presented as mean ± SD or n (%) with p-values from t-test or Pearson chi-squared test.Figure 1.Hospitalization rates according to immunosuppression status in the overall study population.P-values from Poisson regression models.

Baseline characteristics according to immunosuppression status.

Values are presented as mean ± SD or n (%) with p-values from t-test or Pearson chi-squared test.

Hospitalization rates according to immunosuppression status in the overall study population.

P-values from Poisson regression models.

The DAN-RSV trial was a pragmatic, open-label randomized clinical trial conducted during the 2024/25 northern hemisphere winter. Adults aged ≥60 years were enrolled (Nov-Dec 2024) and randomized 1:1 to RSVpreF or no vaccine; only the RSVpreF arm were required to attend a study visit. Baseline and outcome data were obtained from nationwide registries. IS was defined using ICD10 or procedure codes and required ≥1 hospital encounter . Follow-up was from 14 days after vaccination/scheduled visit until May 31, 2025. The primary endpoint was hospitalization for RSV-related respiratory tract disease (RTD); secondary endpoints included hospitalizations for any respiratory and cardio-respiratory disease.Figure 2.Vaccine effectiveness of RSVpreF compared with no vaccine according to immunosuppression status.Vaccine effectiveness was calculated as (1-incidence rate ratio*100%. Interaction p-values were estimated using a Poisson model with a sub-group-by-randomized treatment interaction term included. Abbreviations: PY = person-years; RSVpreF = respiratory syncytial virus prefusion F protein-based vaccine; VE = vaccine effectiveness.

Vaccine effectiveness of RSVpreF compared with no vaccine according to immunosuppression status.

Vaccine effectiveness was calculated as (1-incidence rate ratio*100%. Interaction p-values were estimated using a Poisson model with a sub-group-by-randomized treatment interaction term included. Abbreviations: PY = person-years; RSVpreF = respiratory syncytial virus prefusion F protein-based vaccine; VE = vaccine effectiveness.

Among 131,276 participants (65,642 RSVpreF; 65,634 no vaccine), 5,199 (4.0%) were IS. IS participants were older with more comorbidities (Table 1), as well as higher hospitalization rates (Fig. 1). Among the unvaccinated group, RSV-related RTD hospitalization rates were >9 times higher among IS persons (9.26; 4.96/0.5) (Fig. 2). Incidence of RSV-related RTD was lower in the RSVpreF group than in the no-vaccination group, with consistent effects regardless of baseline IS status (1.85 events vs. 4.68 events per 1000 person-years (PY); vaccine effectiveness (VE) 60.5% [95% CI: -147.3 to 96.1] in participants with IS compared with 0.04 events vs. 0.50 events per 1000 PY; VE 92.3% [95% CI: 48.8 to 99.8] in those without; pinteraction = 0.22). Consistent beneficial effects on hospitalization rates for were observed in the RSVpreF group vs no vaccine for other outcomes (p for interaction >0.05 for all).

In adults ≥60 years, RSVpreF vaccination reduced hospitalizations for RSV-related cardio-respiratory disease, with consistent effects across immunosuppression subgroups. High rates of severe RSV related disease support the need for vaccination in this population.

All Authors: No reported disclosures