Vaccine Prevention of Maternal Cytomegalovirus Infection

Abstract

Congenital infection with cytomegalovirus (CMV) is associated with auditory, cognitive, and neurologic impairment in newborns. An effective vaccine for the prevention of CMV infection has remained elusive since trials began more than 30 years ago. Clinical trials begun in the 1990s showed that a new vaccine that was based on CMV envelope glycoprotein B with a new adjuvant, MF59 (a squalene-in-water emulsion) was immunogenic and had acceptable adverse event profiles. This phase 2, randomized, double-blind, placebo-controlled clinical trial compared the efficacy and safety of this vaccine with placebo in a population of women of childbearing age who had a high rate of incident CMV infection. The study subjects, 464 CMV-seronegative women, were randomized to receive either the CMV vaccine (n = 234) or placebo (n = 230) at 0, 1, and 6 months after delivery. The relative risk of infection with CMV was estimated with Cox proportional-hazards modeling after adjusting for potential confounders. Following a scheduled interim review, the data showed that the vaccine had crossed the preset boundary (P = 0.0197) for efficacy and a recommendation was made to stop the study prematurely. At a minimum of 1 year of follow-up, 49 study subjects had confirmed infections. Of these, 18 occurred in the vaccine group and 31 in the placebo group. Analysis with the Kaplan-Meier method showed that patients in the vaccine group were more likely to remain uninfected during a 42-month period (P = 0.02). Rates of infection per 100 person-years were 3.3 in the vaccine group and 6.6 in the placebo group, indicating an overall vaccine efficacy of 50% (95% confidence interval, 7%-73%). Congenital CMV infection was detected in 1% of infants (1/81) born to mothers in the vaccine group and in 3% of infants (3/97) born to mothers in the placebo group (P = 0.41). All such infections resulted from maternal infection during pregnancy. Although there were more local adverse reactions (pain, warmth, erythema, and induration) and systemic reactions (fever, chills, myalgia, and arthralgia) in the vaccine group compared to the placebo, there was no statistically significant difference in serious adverse events. The investigators conclude from these findings that CMV glycoprotein B vaccine may confer protection against CMV infection in young women and congenital CMV in their infants. Future studies are needed to confirm these data.