New England Journal of Medicine
Volume 360 – March 19, 2009 – Number 12
http://content.nejm.org/current.shtml

Editorial
One Step Closer to a CMV Vaccine
C. L. Dekker and A. M. Arvin
“In this issue of the Journal, Pass and colleagues describe the results of a phase 2 trial of a vaccine containing recombinant cytomegalovirus (CMV) glycoprotein B subunit antigen combined with MF59 adjuvant for the prevention of CMV infection in seronegative women of childbearing age.1 The primary end point was the time to CMV infection in the women. Their report of 50% vaccine efficacy (95% confidence interval, 7 to 73) is a promising development in the long search for an effective vaccine to protect against congenital CMV infection…”

Vaccine Prevention of Maternal Cytomegalovirus Infection
Robert F. Pass, M.D., Changpin Zhang, M.D., Ashley Evans, M.D., Tina Simpson, M.D., William Andrews, M.D., Meei-Li Huang, Ph.D., Lawrence Corey, M.D., Janie Hill, R.N., Elizabeth Davis, R.N., M.P.H., Cynthia Flanigan, B.S., and Gretchen Cloud, M.S.
ABSTRACT
Background: Congenital infection with cytomegalovirus (CMV) is an important cause of hearing, cognitive, and motor impairments in newborns.

Methods: In this phase 2, placebo-controlled, randomized, double-blind trial, we evaluated a vaccine consisting of recombinant CMV envelope glycoprotein B with MF59 adjuvant, as compared with placebo. Three doses of the CMV vaccine or placebo were given at 0, 1, and 6 months to CMV-seronegative women within 1 year after they had given birth. We tested for CMV infection in the women in quarterly tests during a 42-month period, using an assay for IgG antibodies against CMV proteins other than glycoprotein B. Infection was confirmed by virus culture or immunoblotting. The primary end point was the time until the detection of CMV infection.

Results: We randomly assigned 234 subjects to receive the CMV vaccine and 230 subjects to receive placebo. A scheduled interim analysis led to a stopping recommendation because of vaccine efficacy. After a minimum of 1 year of follow-up, there were 49 confirmed infections, 18 in the vaccine group and 31 in the placebo group. Kaplan-Meier analysis showed that the vaccine group was more likely to remain uninfected during a 42-month period than the placebo group (P=0.02). Vaccine efficacy was 50% (95% confidence interval, 7 to 73) on the basis of infection rates per 100 person-years. One congenital infection among infants of the subjects occurred in the vaccine group, and three infections occurred in the placebo group. There were more local reactions (pain, erythema, induration, and warmth) and systemic reactions (chills, arthralgias, and myalgias) in the vaccine group than in the placebo group.

Conclusions: CMV glycoprotein B vaccine has the potential to decrease incident cases of maternal and congenital CMV infection. (ClinicalTrials.gov number, NCT00125502 [ClinicalTrials.gov] .)