Phase 1 Safety and Immunogenicity Study of a Respiratory Syncytial Virus Vaccine with an Adenovirus 26 Vector Encoding Pre-Fusion F (Ad26.RSV.preF) in adults 60 years and older.

Background. Despite the high disease burden of respiratory syncytial virus (RSV) in older adults, there is no approved vaccine. We evaluated the experimental RSV vaccine, Ad26.RSV.preF, a replication-incompetent adenovirus 26 vector encoding the F protein stabilized in prefusion conformation. Methods. This phase 1 clinical trial was performed in healthy adults aged >= 60 years. Seventy-two participants received 1 or 2 intramuscular injections of low-dose (LD; 5 x 10(10) vector particles) or high-dose (HD; 1 x 10(11) vector particles) Ad26.RSV.preF vaccine or placebo, with approximately 12 months between doses and 2-year follow-up for safety and immunogenicity outcomes. Results. Solicited adverse events were reported by 44% of vaccine recipients and were transient and mild or moderate in intensity. No serious adverse events were related to vaccination. After the first vaccination, geometric mean titers for RSV-A2 neutralization increased from baseline (432 for LD and 512 for HD vaccine) to day 29 (1031 for LD and 1617 for HD). Pre-F-specific antibody geometric mean titers and median frequencies of F-specific interferon gamma-secreting T cells also increased substantially from baseline. These immune responses were still maintained above baseline levels 2 years after immunization and could be boosted with a second immunization at 1 year. Conclusions. Ad26.RSV.preF (LD and HD) had an acceptable safety profile and elicited sustained humoral and cellular immune responses after a single immunization in older adults.