Findings from the ongoing Adult Respiratory Syncytial Virus phase 3 trial suggest RSVPreF3 OA vaccine is effective and safe for individuals aged 60 years and older.
A single dose of an AS01E-adjuvanted RSV prefusion F protein–based candidate vaccine (RSVPreF3 OA) prevented lower-respiratory-tract disease, respiratory syncytial virus (RSV)-related acute respiratory infection, and severe RSV-related lower-respiratory-tract disease in adults 60 years of age or older, according to the results of a study recently published recently in The New England Journal of Medicine.
Prevention was observed, regardless of RSV subtype and the presence of underlying coexisting conditions and RSV subtype.
RSV infection can cause lower-respiratory-tract disease, which can lead to exacerbation of underlying diseases, hospitalization, and death in older adults or those with coexisting conditions. Despite the severity of RSV infection, which accounted for an estimated 5.2 million cases of acute respiratory infection and 33,000 in-hospital deaths among adults 60 years or older in 2019, there is no licensed vaccine against RSV infection.
Most RSV vaccine candidates being evaluated in clinical trials target the RSV F glycoprotein, which mediates host-cell entry and viral fusion, elicits neutralizing antibodies, and is highly conserved across the RSV subtypes A and B. RSVPreF3 OA, a candidate RSV vaccine for older adults, contains F protein stabilized in its prefusion conformation, which exposes epitopes targeted by neutralizing antibodies.
Investigators designed the ongoing, international, placebo-controlled Adult Respiratory Syncytial Virus (AReSVi-006) phase 3 trial (NCT04886596) to assess the efficacy and safety of a single dose of RSVPreF3 OA for adults aged 60 years and older. Efficacy was measured against RSV-related acute respiratory infection and severe RSV-related lower-respiratory-tract disease. Participants were randomly assigned, in a 1:1 ratio, a single dose of RSVPreF3 OA or a placebo before the RSV season.
The AReSVi-006 phase 3 trial is being conducted in 17 countries in Africa, Asia, Europe, Australia, and North America. Investigators will follow participants for 3 consecutive RSV seasons in the Northern Hemisphere and at least 2 consecutive seasons in the Southern Hemisphere. The following results represent the first RSV season in the Northern Hemisphere.
The study included 24,966 participants enrolled in the trial between May 25, 2021, and January 31, 2022. Of these, 12,467 received 1 dose of RSVPreF3 OA and 12,499 received the placebo. Over a median follow-up period of 6.7 months, vaccine efficacy against reverse-transcriptase polymerase chain reaction-confirmed RSV-related lower-respiratory-tract disease was 82.6% (96.95% confidence interval [CI], 57.9 to 94.1), with 7 cases (1.0 per 1000 participant-years) in the vaccine group and 40 cases (5.8 per 1000 participant-years) in the placebo group. These results support the efficacy of the vaccine over an entire RSV season, as vaccine efficacy was observed throughout the median follow-up period of 6.7 months,
Vaccine efficacy was 71.7% (95% CI, 56.2 to 82.3) against RSV-related acute respiratory infection and 94.1% (95% CI, 62.4 to 99.9) against severe RSV-related lower-respiratory-tract disease. Vaccine efficacy was similar against the RSV A and B subtypes. For RSV-related acute respiratory infection, efficacy was 71.9% against subtype A and 70.6% against subtype B. Efficacy against RSV-related lower-respiratory-tract disease was 84.6% for subtype A and 80.9% for subtype B. Vaccine efficacy was consistenly high among participants aged 60 to 69 years and those aged 70 to 79 years, among prefrail older adults, and those with coexisting conditions.
Although the RSVPreF3 OA vaccine was more reactogenic than the placebo, most reported adverse events (AEs) were mild-to-moderate in severity. Incidence of serious AEs and potential immune-mediated diseases were similar in the 2 groups. Therefore, a single dose of RSVPreF3 OA vaccine had an acceptable safety profile. Investigators still advise careful monitoring, as larger numbers of individuals are vaccinated.
The results indicated that, regardless of RSV subtype and presence of underlying condition, a single dose of RSVPreF3 OA vaccine prevented RSV-related acute respiratory infection and lower respiratory-tract-disease and severe RSV-related lower-respiratory-tract disease in adults aged 60 years and older. These findings are significant, as an effective RSV vaccine could affect the burden of RSV-associated illness in older adults.
The authors suggested that the RSVPreF3 OA vaccine may protect vulnerable older adults, though they noted that vaccine efficacy estimates against RSV-related lower-respiratory-tract disease in the oldest age group (≥ 80 years) and in frail participants require a longer follow-up.
The ongoing trial will also evaluate the durability of protection beyond the first RSV season and the necessity of annual revaccination.
Papi A, Ison JM, Langley DG, et al. Respiratory syncytial virus prefusion F protein vaccine in older adults. The New England Journal of Medicine. 2023;338(7):595-608. doi:10.1056/NEJMoa2209604