Cytomegalovirus Cell-Mediated Immunity

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.

Inclusion Criteria:

- Parent/legal guardian and subjects who understand and sign the assent as well as
consent forms for this study.

- Subjects who qualify for the Division of Microbiology and Infectious Diseases, NIAID,
NIH (DMID) study 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," will be
eligible for the initial pre-vaccination blood draw.

- Subjects who meet all inclusion criteria for the DMID 04-039 study and who are
vaccinated will be allowed to participate in the remaining portions of this study.

Exclusion Criteria:

All subjects who are ineligible for the main DMID 04-039 study will not be eligible for
the cell-mediated immunity sub-study.