The findings have supported the launch of a phase 3 trial called EVERGREEN, which is now underway.
CYPRESS, a phase 2b proof-of-concept trial presented at IDWeek 2021, has demonstrated that Janssen’s Ad26.RSV.preF-based vaccine produces a robust immune response and effectively prevents respiratory syncytial virus (RSV)-mediated lower respiratory tract disease (LRTD) in older adults.
Although RSV is responsible for about 130,000 to 180,000 hospitalizations a year in the United States and upwards of 13,000 deaths, it is often underrecognized in older adults because adult physicians don’t always consider the diagnosis, according to Ann R. Falsey, MD, professor in the department of medicine, infectious diseases, at University of Rochester Medical Center, and presenting author of the study.
With no licensed RSV vaccine currently available, investigators sought to develop an immunization to prevent RSV-LRTD in adults aged > 65 years and test it in a randomized, double-blind, placebo-controlled trial.
Prior to RSV season, participants were randomized 1:1 to either the study treatment or placebo. Through the end of RSV season, investigators conducted RSV-specific patient-reported Respiratory Infection Intensity and Impact Questionnaires to track symptoms of acute respiratory infection (ARI), and also relied on clinician assessments.
First occurrence of reverse transcription polymerase chain reaction (RT PCR)-confirmed RSV-mediated LRTD was the primary end point, according to any of the following 3 case definitions: (1) ≥ 3 symptoms of lower respiratory tract infection (LRTI), (2) ≥ 2 symptoms of LRTI, or (3) ≥ 2 symptoms of LRTI or ≥1 symptom of LRTI with ≥ 1 systemic symptom. First occurrence of any RT PCR-confirmed RSV-mediated ARI was a key secondary end point.
Exactly 2891 participants were placed into each study arm, for a total of 5782. Investigators included approximately 200 participants in a subset for immunogenicity assessments. Study participants were 92.5% white and 57.7% female, with a median age of 71 years.
For case definitions 1, 2, and 3, vaccine efficacy was 80% (94.2% CI, 52.2-92.9%), 75% (50.1-88.5%), and 69.8% (43.7-84.7%), respectively, with all P values < 0.001. For the secondary end point, efficacy for any RSV-mediated ARI was 69.8% (95% CI, 42.7-85.1%).
“In the vaccine arm of the immunogenicity subset, geometric mean fold increase in antibody titers 14 days after vaccination was 13.5 for RSV neutralizing antibodies and 8.6 for RSV prefusion F-specific binding antibodies,” investigators reported. “Median frequency of RSV-F-specific INFγ T-cells increased from 34 to 444 SFC/106 PBMC 14 days after vaccination in the vaccine arm; no relevant changes were observed in the placebo arm.”
Overall, the Ad26.RSV.preF-based vaccine elicited a robust humoral and cellular immune response in the older adult study population and proved highly effective in preventing against RSV-mediated LRTD. A phase 3 trial called EVERGREEN is now underway, according to Falsey.
The study, “Efficacy and immunogenicity of an Ad26.RSV.preF-based vaccine in the prevention of RT-PCR-confirmed RSV-mediated lower respiratory tract disease in adults aged ≥65 years: a randomized, placebo-controlled, phase 2b study,” was presented virtually at IDWeek 2021, held September 29-October 3, 2021.