Impact of Egg-Based and Cell-Based Vaccine Platforms on Immune Responses to Repeated Influenza Vaccination

Summary

The goal of this clinical trial is to learn how different types of influenza (flu) vaccines affect the body's immune response over time. Researchers want to understand whether receiving egg-based flu vaccines, cell-based flu vaccines, or a combination of both influences how the immune system responds to future flu vaccinations. The main questions this study aims to answer are: 1. Does a person's previous flu vaccine type affect their immune response to a later flu vaccine? 2. Do repeated vaccinations with the same vaccine platform or switching between vaccine platforms produce different antibody responses? 3. How do different vaccination histories affect flu-specific immune cells and protection against different influenza strains? Participants will be randomly assigned to receive one of four vaccine combinations: * Egg-based vaccine followed by egg-based vaccine * Egg-based vaccine followed by cell-based vaccine * Cell-based vaccine followed by cell-based vaccine * Cell-based vaccine followed by egg-based vaccine Researchers will compare immune responses among these groups. Participants will: * Complete a baseline survey about demographics, vaccination history, medical history, and household information. * Receive a first seasonal influenza vaccination (egg-based or cell-based, depending on random assignment). * Provide blood samples before vaccination and several times afterward to measure immune responses. * Receive a second study influenza vaccination approximately 3 months after the first vaccination. * Continue providing blood samples after the second vaccination. * Complete brief follow-up surveys about health changes, additional vaccinations, and influenza-like illness during the study. Blood samples will be collected up to eight times during each study year: 1. Before or on the day of the first vaccination 2. About 1 week after the first vaccination 3. About 1 month after the first vaccination 4. About 3 months after the first vaccination (the second vaccination will be given at this visit) 5. About 1 week after the second vaccination 6. About 1 month after the second vaccination 7. About 3 months after the second vaccination 8. About 6 months after the second vaccination Participants may be observed for approximately 15 minutes after vaccination, consistent with routine vaccination practices. Prior to the second vaccination, participants will be evaluated for any reasons that might make vaccination unsafe or require postponement. Participants who are able to become pregnant will complete a urine pregnancy test before the second vaccination. Participants who are pregnant or have a positive pregnancy test will not receive the second study vaccination but may continue study follow-up activities, including blood collection and surveys. Participation in each study year lasts up to 10 months. Participants may choose to continue participating annually for up to 7 years. Blood samples and related study data may be stored in a secure research biorepository for future studies related to infectious diseases, immunology, vaccine responses, and other health conditions. Stored samples will be coded to protect participant privacy, and identifying information will not be shared without appropriate approvals and participant authorization