Safety and Immunogenicity of a Revaccination With a Respiratory Syncytial Virus Prefusion F Vaccine in Older Adults: A Phase 2b Study

Background In the previous (parent) study, 2 doses of different formulations of an investigational vaccine against respiratory syncytial virus (RSVPreF3 OA) were well tolerated and immunogenic in older adults. This multicenter phase 2b extension study assessed safety and immunogenicity of a revaccination (third) dose of the 120 & mu;g RSVPreF3-AS01E formulation.Methods In total, 122 older adults (60-80 years), previously vaccinated with 2 doses of RSVPreF3-AS01E formulations (containing 30, 60, or 120 & mu;g RSVPreF3 antigen), received an additional 120 & mu;g RSVPreF3-AS01E dose 18 months after dose 2. Vaccine safety was evaluated in all participants up to 6 months and immunogenicity in participants who received 120 & mu;g RSVPreF3-AS01E doses until 1 month after dose 3.Results Similar to the parent study, mostly mild-to-moderate solicited adverse events and no vaccine-related serious adverse events or potential immune-mediated disorders were reported. Neutralizing titers and cell-mediated immune responses persisted for 18 months after 2-dose vaccination. Dose 3 increased RSV-specific neutralizing titers against RSV-A and RSV-B and median CD4+ T-cell frequencies. After dose 3, RSV-specific neutralizing titers but not CD4+ T-cell frequencies were below levels detected 1 month after dose 1.Conclusions Revaccination with 120 & mu;g RSVPreF3-AS01E 18 months after dose 2 is well tolerated and immunogenic in older adults.Clinical Trials Registration NCT04657198; EudraCT, 2020-000692-21. This phase 2b extension study demonstrated an acceptable safety profile and robust immunogenicity of a third, revaccination, dose of an adjuvanted vaccine against respiratory syncytial virus administered 18 months after the second dose in older adults aged & GE;60 years. Respiratory syncytial virus (RSV) is a common, contagious seasonal virus causing respiratory tract infections. In older adults, RSV can cause serious respiratory illnesses or worsen underlying medical conditions such as chronic diseases of the lungs or heart failure. Severe disease may lead to hospitalization, increased need for oxygen, and ventilatory support. However, several vaccines against RSV in older adults have recently been licensed in the United States and European Union.This study evaluated safety and immune responses after revaccination (third dose) with an adjuvanted vaccine against RSV in older adults aged 60-80 years, who had received 2 doses of the vaccine with a similar adjuvanted formulation in a previous (parent) study. Revaccination was done with the licensed vaccine formulation, which was also selected for further investigation in several phase 3 clinical trials.This study found that immune responses against RSV persisted above prevaccination levels for at least 18 months after the second vaccination in the parent study. The third vaccine dose was well tolerated and recalled the immune responses in older adults. Together with the ongoing confirmatory clinical trials, these results help better characterize this RSV vaccine, in terms of safety and RSV-specific immune responses elicited in older adults.