• Immunogenicity based on CMV specific cell-mediated immunity. [ Time Frame: Measured 30 days after the first dose, 30 days after the second dose, 30 days after the third dose and 7 months after the third dose of vaccine. ] [ Designated as safety issue: No ]
  

Cytomegalovirus (CMV) is an important cause of morbidity and occasional mortality in congenitally infected infants and immuno-compromised children and adults, especially human immunodeficiency virus (HIV)-infected individuals and transplant recipients. Newborn infants represent a particularly high-risk group. This study of cell-mediated immune responses to cytomegalovirus GB/MF59 vaccine is a substudy of DMID protocol 04-039, "A Randomized, Double-blind, Placebo-controlled, Phase II Study to Assess the Safety and Efficacy of the Cytomegalovirus gB/MF59 Vaccine in Preventing Systemic Cytomegalovirus Infection in Healthy Adolescent Females." This vaccine trial is designed to test the safety and efficacy of the CMV gB/MF59 vaccine by establishing a reproducible, functional cell-mediated immune response assay to evaluate the magnitude and functional capacity of T cells responding to monovalent subvirion CMV and to evaluate the percent of subjects demonstrating a CD4+ and/or CD8+ response after the first, second, and third dose of vaccine. Primary goals of this study are to assess whether injection with 3 doses of the CMV gB/MF59 vaccine induces significant CD4+, CD8+ and/or regulatory T cell immune responses; to evaluate the boosting affect of gB/MF59 on the CMV-specific T cell responses after each of 3 doses of vaccine; to evaluate the persistence of CMV-specific T cell responses after vaccination; and to evaluate CMV-specific T cell responses in subjects that seroconvert during the vaccine trial. New techniques for the enumeration and characterization of antigen specific T cells are now available that will facilitate a precise analysis of the magnitude and functional capacity of influenza virus-specific T cells. All subjects enrolled in the CMV gB/MF59 trial at Vanderbilt and Cincinnati study sites will be eligible for enrollment in the cell-mediated immune response sub-study. Blood draws for assessment of cellular immune response will be obtained in 3 phases. Phase 1, N=50: at visit 1, the initial 100 consented subjects to recruit approximately 50 seropositive subjects (based on a 60 percent seropositive rate). Samples from this phase of the study will be used to establish the optimal conditions for the assay and to compare natural infection with vaccine induced T cell responses. This phase of the study will be performed at the Vanderbilt site only. Phase 2, N=50-100: at day 0 (before 1st dose of vaccine), day 30 (before the second dose of vaccine), day 60 (1 month after the second dose of vaccine), day 210 (1 month after the last dose of vaccine), and day 390 (7 months after the last dose of vaccine). Samples from this phase will be used to evaluate the boosting affect of gB/MF59 after each of 3 doses of vaccine and to evaluate the persistence of CMV-specific T cell responses. Phase 3: at each visit (S1-S8) for those subjects that seroconvert (i.e. if subject seroconverts at visit 10 blood will be obtained at visits S1-S8). These samples will be used to compare CMV-specific responses in subjects that either did or did not receive the vaccine and seroconvert during the study. These time points are based on the vaccine study design and the previous work evaluating T cell responses to vaccination 1 month and 6 months after immunization. Researchers will collect 30 ml of blood per draw in this trial enrolling up to 100 healthy adolescent females 12-17 years of age, inclusive. Blood volumes were determined to ensure sufficient numbers of cells to establish stimulation protocols and evaluate cell-mediated immune responses. The study duration will be 43 months. Subject duration will be 31 months, unless the subject seroconverts and enrolls into the shedding study. This study is linked to DMID protocol 04-039.