Janssen RSV Vaccine for Older Adults Drives Robust Cellular Immune, Humoral Response

A phase 2b proof-of-concept trial evaluating a vaccine against respiratory syncytial virus (RSV) demonstrated efficacy as high as 80% in preventing RSV-mediated lower respiratory tract infections in older adults. Janssen presented the data from its CYPRESS trial on the Ad26.RSV.preF-based vaccine during IDWeek 2021, which wrapped on Sunday, October 3, 2021.

RSV, a leading cause of bronchitis, bronchiolitis, and pneumonia, affects more that 64 million people globally each year. In the US, according to the Centers for Disease Control and Prevention (CDC) the infection causes on average 58 000 hospitalizations a year among children younger than age 5 years and between 100 and 500 deaths. Among adults aged 65 years and older, hospitalizations average 177 000 and deaths reach 14 000 annually, according to a Janssen statement.

There is currently no vaccine against RSV nor is there a widely available antiviral treatment. Janssen in 2019 was granted FDA Breakthrough Therapy Designation for the investigational prophylactic RSV vaccine as the CYPRESS trial was under way.

The randomized, double-blind placebo-controlled CYPRESS trial enrolled 5782 participants aged ≥ 65 years. Participants were randomized 1:1 (2891 in each study arm) to receive the Janssen adenovirus-based vaccine or placebo. Active and mock vaccines were administered just before the beginning of RSV season.

Disease symptoms throughout a single season were collected through investigator-conducted RSV-specific patient-reported Respiratory Infection Intensity and Impact Questionnaires and/or clinician’s assessment

The study’s primary endpoint was a first occurrence of reverse transcription polymerase chain reaction (RT PCR)-confirmed RSV-mediated LRTD across 3 case definitions

• 1. ≥3 symptoms of lower respiratory tract infection (LRTI)
• 2. ≥ 2 symptoms of LRTI
• 3. ≥ 2 symptoms of LRTI or ≥1 symptom of LRTI with ≥ 1 systemic symptom

First occurrence of any RT PCR-confirmed RSV-mediated acute respiratory infection (ARI) was a key secondary end point.

Investigators included a subset of approximately 200 participants in a subset for immunogenicity assessment and 695 for safety assessments. Study participants were 92.5% white and 57.7% female, with a median age of 71 years.

Results

For the 3 case definitions, vaccine efficacy was reported as follows (all P values <.001):

• 1. 80% (94.2% CI, 52.2-92.9%)
• 2. 75% (50.1-88.5%)
• 3. 69.8% (43.7-84.7%)

Efficacy for any RSV-mediated ARI, the secondary endpoint, was 69.8% (95% CI, 42.7-85.1%).

The authors state that humoral and cellular response to the Ad26.RSV.preF-based vaccine was robust, with a 13.5-fold increase in antibody titers observed 14 days after vaccine administration in the study cohort of adults aged ≥ 65 years.

“RSV remains a major global public health concern and a cause of serious respiratory illness in all age groups,” said Ann R. Falsey, MD, professor of medicine, University of Rochester School of Medicine, in the company statement. Falsey, who presented the results at IDWeek, added “The positive efficacy results from the CYPRESS study reinforce the potential of this investigational RSV vaccine in preventing serious disease resulting from RSV in older adults.”

Based on the positive phase 2B CYPRESS findings, Janssen subsequently announced the initiation of the phase 3 EVERGREEN study that will compare the investigational vaccine vs placebo in approximately 23 000 adults aged ≥ 60 years throughout North America and countries in Europe, Asia, and the southern hemisphere.

Source: 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.