This prospective, single-arm study is designed to understand the mechanisms that lead to a loss of response to influenza vaccine in older adults through the establishment of the FluVax3 cohort of healthy older adults. In this study, the investigators will perform comprehensive profiling of blood antibodies and immune cells over time, and associate specific age-related immune alterations with vaccine responder or non-responder status. This will allow the investigators to pinpoint biological pathways that can be targeted to enhance vaccine efficacy and that can also help the investigators progress towards developing a universal influenza vaccine. The results are expected to provide the foundation for new approaches to improve overall vaccine efficacy and protection in older adults, an outcome of significant public health relevance considering the vulnerability of this population.~In this study, a total of sixty-six (66) healthy adults aged 65 years and older who have not received influenza vaccination for the approaching influenza season will be enrolled in the study and vaccinated with influenza vaccines approved by the U.S Food and Drug Administration (FDA) and recommended by the Centers for Disease Control and Prevention (CDC) for individuals ≥65 years. All participants receive influenza vaccine during the 2022-23, 2023-24, and 2024-25 influenza seasons. Participants will receive Fluzone® Quadrivalent High-Dose vaccine during the 2022-23 flu season and FLUAD® Quadrivalent during the 2023-24 flu season. The researchers of this proposed study will reevaluate the CDC recommendations and vaccine availability for the 2024-25 season to determine the third vaccine. The study sample will be drawn from the population of healthy older participants in the catchment area of UConn Health in Farmington, CT.~Study participation will involve six study visits around the flu vaccine each year and one final study visit for a total of nineteen study visits over three years. Blood samples will be collected at sixteen study visits for transcriptional, epigenetic and biological analyses pre- and post-vaccination. Nasal swab and stool samples will also be collected from participants at seven time-points across the study period. These microbiome samples will be stored and used in future research. The study is not designed to assess safety or tolerability of the influenza vaccines administered as part of this proposed study.~This project will yield an unparalleled dataset from healthy older adults that will be used to identify fundamental mechanisms, cell populations, and pathways associated with durable protective antibody immune responses, and lack thereof, upon influenza vaccination. In sum, this study will reveal the mechanistic alterations that explain the heterogeneity in response to vaccines observed in older individuals. Understanding this heterogeneity opens the possibility of stratifying older adults for personalized vaccines. In addition, understanding the mechanistic overlap between the correlates of responsiveness to three different influenza vaccines will advance the ultimate development of a universal influenza vaccine, which is a key focus of NIAID's influenza research program. Finally, this study will generate a considerable amount of transcriptional and functional data related to the outputs of key innate immune and T/B-cell subsets involved in responses to influenza vaccines in older adults. These data will collectively become an important resource for future studies focused on the older adult immune system in health and disease.
This is a prospective, single-arm study designed to understand the mechanisms that lead to a loss of response to influenza vaccine in older adults. The investigators will recruit and longitudinally follow a cohort of 66 older adults (65 years and older) who will receive three different influenza vaccines over three annual influenza seasons. Blood samples will be collected from the participants at each of the sixteen study visits over three years. Nasal swab and stool samples will also be collected from participants at seven time-points across the study period. The study is not designed to assess safety or tolerability of the influenza vaccines administered as part of this study.