Cytomegalovirus Cell-Mediated Immunity
Condition: Cytomegalovirus Infections
MeSH terms: Cytomegalovirus Infections
Study type: Observational

Summary: 
      Cytomegalovirus (CMV) is an important cause of illness and occasional deaths in infants who
      catch the virus before they are born, in newborns, and in children and adults who have weak
      immune systems. The purpose of this study is to look at how the CMV vaccine works in the
      blood. This study is being done along with the main CMV gB/MF59 vaccine study that looks at
      how the overall body reacts to the vaccine. Participants will include up to 100 healthy
      adolescent female subjects aged 12 to 17 years who were vaccinated in study 04-039 and 100
      subjects that were screened for 04-039 to participate as controls. Study procedures will
      include up to 6 blood draws taken over a 13 month period. Participation will be about 31
      months (unless the patient enrolls into the shedding study).
    

Detailed description: 
      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 Division of Microbiology and Infectious
      Diseases, NIAID, NIH, DHHS (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. 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. 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.
    

Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        A convenience sample of up to 100 healthy participants, ages 12-17 years, who were
        vaccinated in 04-039. Additionally, 100 screened subjects enrolled to serve as
        positive/negative controls.
      
Biospecimen description: 
      Blood.
    
Keywords: cytomegalovirus, CMV, cell-mediated immunity, children, sub-study