Influenza and pneumonia are the fourth leading cause of death among people aged over 65 years. Influenza also leads as a cause of catastrophic disability, greatly affecting the quality of life of elderly persons. In the United States alone, an estimated 10 billion dollars is spent annually due to the impact of influenza, and this will rise as the population of seniors rapidly expands. Thus, influenza vaccination is recommended for elderly adults. Although it is cost-effective, influenza vaccination only prevents infection in 30 percent-40 percent of those aged over 65, compared to 70 percent-90 percent of those under 65. Reduced influenza vaccine efficacy and greater morbidity and mortality are thought to be largely due to immune senescence, but the underlying mechanism remains poorly understood. A better understanding of immune senescence can ultimately translate into improved effectiveness for a variety of vaccines, including vaccines against bioterrorist attack (such as small pox vaccine), and thereby bring huge advances in disease prevention and billions in cost savings. The commercially available influenza vaccine used in the United States contains inactivated split viral particles of influenza B and two subtypes of influenza A. These vaccines are cost-effective, but far from perfect; up to 61 percent of vaccinated elderly people acquire influenza infection nonetheless. The safety and cost effectiveness of the licensed split influenza virus vaccine is established, reducing researchers' incentive to further improve the vaccine or define the difficult and expensive-to-measure T cell-mediated immunity to it. The ultimate goal of this proposed non-randomized, open-label study is to improve vaccine efficacy in order to reduce morbidity and mortality from influenza and other infectious diseases in elderly people. The primary objective is to examine the safety and immunogenicity of vaccine strategies to enhance the Type 1 Helper Cells (Th1) response by booster at the peak of Influenza specific (IS)-Th1 expansion following first vaccination. The frequency of IS-Th1 and the antibody level on days 7 and 28 will be used as the two main indicators of immunogenicity, although CD8+ T cell response will also be analyzed. The safety profile to be assessed includes immediate adverse events, solicited local and systemic events, and unsolicited adverse events. Seventy-four healthy individuals who are living independently in the communities surrounding the study site will be invited to participate in the trial. Participants between the ages of 21 and 40 years (young cohort) and those 60 years and older (elderly cohort) will be recruited. Participants will be considered active in the trial for 3 months post vaccination. A telephone follow-up visit will be scheduled at 6 months post-vaccination. Four groups of subjects will be recruited: 1 control group (Group 1) and 3 experimental groups (Group 2, Group 3, and Group 4). This study is linked to DMID protocol 05-0125. Protocol 05-0125 contains Part II of this study.