The respiratory syncytial virus prefusion F protein vaccine attenuates the severity of respiratory syncytial virus-associated disease in breakthrough infections in adults ≥60 years of age

Abstract

Background: Respiratory syncytial virus (RSV) is a contagious pathogen causing acute respiratory infections (ARIs). Symptoms range from mild upper respiratory tract infections to potentially life-threatening lower respiratory tract disease (LRTD). In adults ≥60 years old, vaccine efficacy of a candidate vaccine for older adults (RSVPreF3 OA) was 71.7% against RSV-ARI and 82.6% against RSV-LRTD (AReSVi-006/NCT04886596). We present the patient-reported outcomes (PROs) from the same trial at the end of the first RSV season in the northern hemisphere (April 2022).

Methods: In this phase 3 trial, adults aged ≥60 years were randomized (1:1) to receive one dose of RSVPreF3 OA vaccine or placebo. PROs were assessed using InFLUenza Patient-Reported Outcome (FLU-PRO), Short Form-12 (SF-12), and EuroQol-5 Dimension (EQ-5D) questionnaires. Peak FLU-PRO Chest/Respiratory scores during the first 7 days from ARI episode onset were compared using a Wilcoxon test. Least squares mean (LSMean) of SF-12 physical functioning (PF) and EQ-5D health utility scores were estimated using mixed effects models.

Results: In the RSVPreF3 OA group (N = 12,466), 27 first RSV-ARI episodes were observed versus 95 in the Placebo group (N = 12,494). Median peak FLU-PRO Chest/Respiratory scores were lower in RSVPreF3 OA (1.07) versus Placebo group (1.86); p = 0.0258. LSMean group differences for the PF and EQ-5D health utility score were 7.00 (95% confidence interval [CI]: -9.86, 23.85; p = 0.4125) and 0.0786 (95% CI: -0.0340, 0.1913; p = 0.1695).

Conclusions: The RSVPreF3 OA vaccine, in addition to preventing infection, attenuated the severity of RSV-associated symptoms in breakthrough infections, with trends of reduced impact on PF and health utility.

Keywords: acute respiratory infections; older adults; patient‐reported outcome; quality of life; respiratory syncytial virus.

FIGURE 1

Median daily FLU‐PRO Chest/Respiratory scores and box‐plot distribution of the maximum (peak) FLU‐PRO Chest/Respiratory score by study group (mES RT‐PCR‐confirmed RSV‐ARI cohort). Values shown are the median values of the FLU‐PRO Chest/Respiratory scores on Days 1 through 7 of the RSV‐ARI episode (panel A) and the maximum (peak) FLU‐PRO Chest/Respiratory scores observed over the course of the RSV‐ARI episode (Days 1 through 7) (panel B). A higher score indicates a greater severity of symptoms/problems. Note: The minimum and maximum values shown in panel B are across both groups, to maintain blinding of the ongoing study. Data for the other FLU‐PRO domains are presented in Table S3. RSVPreF3 OA, participants receiving RSVPreF3 OA vaccine (27 participants with RSV‐ARI episodes); Placebo, participants receiving placebo (95 participants with RSV‐ARI episodes). FLU‐PRO, InFLUenza Patient‐Reported Outcome; Max, maximum; mES, modified exposed set; Min, minimum; N, number of observations; Q1, 25th percentile; Q3, 75th percentile, RSV‐ARI, respiratory syncytial virus–acute respiratory infection; RT‐PCR, reverse transcription polymerase chain reaction.

FIGURE 2

SF‐12 PF and EQ‐5D utility scores by assessment time and study group (mES RT‐PCR‐confirmed RSV‐ARI cohort). Least squares means were obtained from the longitudinal model featuring the baseline assessment and the assessment during the RSV‐ARI episode including terms for study group, timepoint, and timepoint by study group interaction term. A higher score indicates a higher level of functioning/quality of life. RSVPreF3 OA, participants receiving RSVPreF3 OA vaccine (27 participants with RSV‐ARI episodes); Placebo, participants receiving placebo (95 participants with RSV‐ARI episodes). EQ‐5D, EuroQol‐5 Dimension; LSMeans, Least squares means; mES, modified exposed set; N, number of observations; RSV‐ARI, respiratory syncytial virus–acute respiratory infection; RT‐PCR, reverse transcription polymerase chain reaction; SF‐12 PF, Short Form‐12 physical functioning.