The central hypothesis of this study is that immune responses to vaccination can be quantified by proteomic profiling of serum (and other clinical fluids), and that the host responses to different infectious agents are unique and can be 'fingerprinted' by proteomics. Using influenza virus vaccination, this study proposes to use mass spectrometry platforms to profile and characterize proteins from serum samples obtained from recipients. These samples will be used to develop a proteomic profiling system for monitoring vaccine response and, eventually, early detection/diagnosis of infection. The long-term goal of this approach is to develop tools useful for reducing the morbidity and mortality of influenza from natural and potential bioterrorism-related infections by improving measures of vaccine efficacy and early diagnosis. The primary objective is to use surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry proteomic profiling tools to analyze a series of serum samples obtained from cohorts of young and elderly subjects, before and after trivalent split-virus influenza vaccination, to identify surrogate markers reflective of the immune response. The secondary objective is to use concurrent T-cell activation, cytokine assays, and hemagglutination inhibition (HI) serologic assays to correlate cellular and humoral responses to influenza vaccination with protein profiling changes. Comparisons of the protein profile data with the T-cell activation, cytokine assays, and HI results will be evaluated using multiple classification algorithms, and potential biomarker proteins will be identified by sequencing with either a MALDI-TOF or electrospray ionization mass spectrometer. Study Participants will include healthy adult volunteers between the ages of 21-40, between the ages of 60-89, or 90 years and older, who are living independently in the communities surrounding the 3 study sites in Virginia. There will be 5 study visits, and subjects will be in the trial for up to 1 month. The primary endpoint of the study is to identify surrogate markers reflective of the immune response and to correlate these markers to cellular and humoral responses (demonstrated with T-cell activation, cytokine assays, and the HI serologic assays) to influenza vaccination. The secondary endpoint is safety. Data on the following solicited local reactions (injection site pain, bruising, redness, tenderness, and induration) and solicited systemic reactions (fever, headache, malaise, myalgia, cough, runny nose, chills, vomiting, arthralgia, rash, and diarrhea) will be collected from Day 0-Day 14 and categorized as none, mild, moderate, and severe. Unsolicited adverse events (including serious adverse events) will be collected and categorized throughout the study by severity, duration, and relatedness to the vaccine.