The purpose of this vaccine study is to determine whether a combination vaccine containing a CTl and T-helper epitope, lipidated at the amino terminus will serve to boost the immunity against cytomegalovirus. The protocol will have two phases; the first being amplification of a memory response in seropositive individuals, followed by an immunization of seronegative individuals who have not been productively infected by the virus. To establish safety, a dose escalation study will be done in the group of subjects with prior CMV immunity. The justification for using this group is that they represent a primary target population for an eventual immunization trial in marrow transplant donors. In addition, it is important to establish the safe dosing of this recall immunization, since it is probably more likely to be associated with side effects then the primary immunization. Once a safe dose is established at which an immune recall response occurs, then this dose will be evaluated for safety in primary immunization regimen. Here, CMV naove subjects will be immunized using a primary injection followed by 2-3 booster injections. Healthy HLA-A*0201-positive male and female volunteers, aged 18-55, who are CMV-seropositive by standard antibody test (see section 4,13,2) will be randomly assigned to one of four dosage groups. Each group will consist of 10 subjects, 4 each will receive an identical dosage of the CMVpp65-A8201 vaccine containing either HTL PADRE peptide (vaccine A) or HTL Tetanus peptide (vaccine B, see Table 2). Within each dose level, 2 subjects will receive placebo, consisting of formulation buffer (i.e., 5-25% DMSO in PBS), and subject assignments will be blinded to the subjects and investigators. Subjects will be stratified by gender for equal distribution into each subgroup. Groups will be immunized sequentially at escalating doses of 50, 250, 1000, 2500 ig/dose. Vaccine A or B or placebo will be administered by injecting 0.5-1.0 ml s.c. into the upper forearm. A booster injection of the same dose and material will be given 28 days after the initial injection. The booster injection will be given in the same anatomical location as the primary inoculation. Subjects will be followed for 12 months for safety observations and immunologic evaluations. In an attempt to study the primary immune response to the CMVpp65-A*0201 vaccine and to establish its safety when used in a multiple booster regimen, HLA A*201/CMV-seronegative volunteers will be immunized using a dose established to be both safe and immunologically efficacious in trial #1. Six subjects will receive a primary immunization followed by a similar booster injection at 28 days and 56 days post-vaccination. There will be no placebo group. If no immunologic response is detected, then no additional booster will be given. However, if a partial or low level response is detected in a subject, then a third booster will be administered between 84-90 days post-primary vaccination. Subjects will be followed for 12 months for safety observations and immunologic evaluations.
NIH ExPorter
NIH ExPorter