1. In this randomized controlled trial, vaccination with Ad26.RSV.preF-RSV preF protein was associated with significantly reduced respiratory syncytial virus (RSV) infection in older adults compared to placebo.
2. While solicited local and systemic adverse events were higher in the vaccine group than in the placebo group, the frequency of serious adverse events was similar between the two groups.
Evidence Rating Level: 1 (Excellent)
Study Rundown: RSV is a leading cause of lower respiratory tract disease in older adults, with potentially severe complications such as pneumonia and the exacerbation of underlying conditions. There are currently no approved RSV vaccinations. In this phase two randomized controlled trial, the efficacy, immunogenicity, and safety of the Ad26.RSV.preF-RSV preF protein vaccine was evaluated for the prevention of RSV infection in adults over the age of 65. Participants were randomly assigned to receive either one intramuscular vaccine or saline placebo injection and followed for six months or until the end of the RSV season. The incidence of RSV-mediated lower respiratory tract infection was significantly lower in the vaccine group compared to the placebo group. For immunogenicity, titers of neutralizing antibodies against RSV A and RSV B, levels of serum RSV preF IgG antibodies, and RSV-F-specific interferon-γ T-cell frequencies increased in the vaccine group at day 15 and remained above baseline for at least six months. For safety outcomes, the incidence of serious adverse events was not significantly different between groups. Solicited systemic adverse events were more common in the vaccine group compared to the placebo group. As a limitation, the trial was shortened due to the onset of the COVID-19 pandemic. Analysis was conducted on the per-protocol efficacy population, rather than the intention-to-treat protocol, which may bias results. There were also few participants older than 85, and the study was unable to evaluate the safety and efficacy of the RSV vaccine for this age population.
Click to read the study in NEJM
In-Depth [randomized controlled trial]: In this phase two randomized clinical trial, the efficacy and safety of the Ad26.RSV.preF-RSV preF protein vaccine was evaluated. Participants (n=5,782) aged 65 or over in stable health were randomly assigned in a 1:1 ratio to receive either one intramuscular injection of vaccine (n=2,891) or saline placebo (n=2,891). Participants were followed for six months or until the end of the RSV season. The primary outcome was the first occurrence of RSV-mediated lower respiratory tract disease according to one of three definitions: three or more symptoms of lower respiratory tract infection (definition one), two or more symptoms of lower respiratory tract infection (definition two), and either two or more symptoms of lower respiratory tract infection or one or more symptoms of lower respiratory tract infection plus at least one systemic symptom (definition three). For the primary outcome, the vaccine efficacy against illness meeting case definitions one, two, and three were 80% (94.2% Confidence Interval [CI], 52.2 to 92.9; p<0.001), 75% (94.2% CI, 50.1 to 88.5; p<0.001), and 69.8% (94.2% CI, 43.7 to 84.7; p<0.001), respectively. A subset of the study population was evaluated for immunogenicity (n=195). In the vaccine group, the geometric mean titer of RSV A2 and B neutralizing antibodies increased by a factor of over nine at day 15 compared to baseline and remained over four times the baseline value at day 169. The concentrations of serum preF IgG antibodies and RSV-F-specific T-cell frequency were also higher on days 15 and 169. No changes in immunogenicity measures were observed in the placebo group. The incidence of serious adverse events was not significantly different between groups. Solicited systemic adverse events were higher in the vaccine group (41.4%) compared to the placebo group (16.4%). In summary, Ad26.RSV.preF-RSV preF protein vaccine may be useful in reducing the incidence of RSV infection in older adults.
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