Two RSV vaccines for seniors were FDA approved this year and here is an overview of the vaccines and the study data.
Since its identification in 1957, the respiratory syncytial virus (RSV) has been a leading contributor of lower respiratory tract disease (LRTD) in infants, toddlers, and adults greater than 65 years of age or those with comorbid conditions.1 RSV illness accounts for an estimated 177,000 hospitalizations and 14,000 deaths each year in the United States.2,3
Two separate RSV vaccines, RSVPreF3 (Arexvy, GSK) and RSVpreF (Abrysvo, Pfizer) received FDA approval and ACIP endorsement in 2023.4 Both are protein subunit vaccines, targeting the surface viral membrane fusion (F) protein.The F protein initiates viral penetration into host cells by fusing viral and cellular membranes; as disease progresses the F protein causes cells to fuse leading to syncytia. The pre fusion F protein is the active form on the viral surface which is triggered and transforms into the post F protein after binding occurs. The F protein is present in both RSV subtypes A and B and elicits high potency antibody production making it a natural target for vaccination.1
The RSVPreF3 RSV vaccine includes the AS01 adjuvant, which in preliminary studies demonstrated a higher rate of RSV specific CD4+ T cells in older adults.5 In a single phase 3 randomized controlled trial prevention of RSV-associated LRTD was demonstrated across both RSV seasons, though efficacy declined during the 2nd year post vaccination (Table 1). 4,5 The study was not powered to assess efficacy against hospitalizations, severe illness, or death. The trial excluded immunocompromised adults and residents of long term care facilities and had limited numbers of patients > 75 years of age who may benefit from vaccination.Pooled safety data show a higher rate of local/systemic reactions than placebo but an overall low rate of inflammatory neurologic events.4,5
The Pfizer RENOIR trial includes season 1, however the study is ongoing to include RSV season two. Efficacy calculated by cases prevented: 1 - [RSV cases of vaccinated / RSV cases unvaccinated] x 100. Data available for partial season 2 demonstrated efficacy of 78.6% during a partial second RSV season (interim estimate; the second season efficacy will be updated upon study completion).6 Participant frailty was not assessed in this clinical trial (Table 2). The trial was underpowered to demonstrate efficacy against RSV-associated hospitalization and RSV-associated death.
RSV vaccination in older adults decreases RSV-associated LRTD which could reduce RSV-associated hospitalizations and mortality. The low risk of serious adverse effects and potential for co-administration with influenza and COVID-19 vaccination create a favorable risk benefit profile.7 However, questions remain about the durability of vaccine benefit and the potential need for revaccination. It remains unclear whether the noted Afib occurrences were due to random chance, or whether RSV vaccination increases the risk of these events. FDA post-marketing requires both manufacturers to conduct safety studies to evaluate the risk of these adverse events following RSV vaccination.4
CDC recommends that older adults ages ≥60 years may receive a single dose of RSV vaccine using shared clinical decision making. Adults with higher risk of severe disease should be considered for RSV vaccination (Table 3).8 Abrysvo has an indication for pregnant patients 32-36 weeks gestation. Optimally, vaccinations should occur before the onset of the fall and winter RSV season, however seasonality was disrupted by COVID-19 pandemic. For the 2023-2024 RSV season, patients eligible should receive as early as vaccine supply becomes available.4