Objective: To test the efficacy of vaccination with the Towne live attenuated cytomegalovirus vaccine.
Design: A double-blind, randomized, placebo-controlled trial in candidates for renal transplantation. The cytomegalovirus serologic status of both recipients and donors was determined, and the recipients were followed for periods of 6 months to 7 years after transplant.
Setting: A university transplant center.
Patients: The analyses were made on 237 patients who were given either vaccine or placebo, received renal transplants, and were followed for at least 6 months.
Intervention: Subcutaneous inoculation with Towne live attenuated virus or with placebo.
Main Outcome Measures: The presence of cytomegalovirus infection was defined by virus isolation and antibody tests. If infection occurred, a prearranged scoring system for cytomegalovirus disease was used to objectify disease severity.
Results: The vaccine was well tolerated, and there were no discernible long-term adverse effects. Recipients who were originally seropositive did not clearly benefit from vaccination. Protective efficacy was analyzed in the group at highest risk for cytomegalovirus disease: recipients who were seronegative at the time of vaccination and who received a kidney from a seropositive donor. Compared with placebo recipients, vaccinated patients in this group had significantly less severe cytomegalovirus disease, with a significant reduction in disease scores (P = 0.03) and 85% decrease in the most severe disease (95% CI, 35% to 96%), although infection rates were similar. Graft survival at 36 months was improved in vaccinated recipients of cadaver kidneys (8 of 16) compared with unvaccinated recipients (4 of 16) (P = 0.04).
Conclusions: Previous vaccination of seronegative renal transplant recipients with live cytomegalovirus results in reduction of disease severity mimicking the action of naturally derived immunity.