Abstract
In the developed world, cytomegalovirus (CMV) is the most common congenital viral infection, with an overall birth prevalence of 0.6% [1]. Approximately 10% of congenitally infected infants have signs and symptoms of disease at birth, and these symptomatic infants have been reported to have a 40%– 90% risk of subsequent neurologic sequelae, including mental retardation, microcephaly, development delay, seizure disorders, and cerebral palsy [2–4]. Seven percent –to 20% of asymptomatically infected newborns will also demonstrate sequelae, particularly sensorineural hearing loss [5–7]. The public health impact of congenital CMV infection is substantial and underrecognized; although more children suffer from long-term neurodevelopmental handicaps as a result of congenital CMV infection than either Down syndrome or fetal alcohol syndrome [8], awareness unfortunately remains low, particularly among women of childbearing age [9, 10]. An effective vaccine could, by preventing neurological sequelae and other disabilities, provide a newborn with a lifetime of benefit. For that reason, a report from the Institute of Medicine (IOM) of the National Academy of Sciences placed CMV in its highest priority category for vaccine development, concluding that a vaccine would be strongly cost saving [11, 12]. Among the various CMV vaccine candidates currently in clinical trials [13], the most encouraging results to date have been observed in studies of a vaccine based on the immunodominant envelope glycoprotein B (gB). Several clinical trials have been performed using a recombinant form of this protein expressed in Chinese hamster ovary cells, purified and combined with an oil-in-water adjuvant known as MF59 [14–17]. Pass et al recently reported the results of a seminal phase II efficacy trial of the gB-MF59 vaccine conducted at the University of Alabama, Birmingham. This trial was undertaken in adolescent and young adult women. The study population was remarkable for being at a particularly high risk for acquisition of a primary CMV infection, with an annualized seroconversion rate noted in previous studies of 7.8% [18]. This study was a randomized, double-blind, placebo-controlled clinical trial in seronegative women, recruited from post-partum units. A substantial proportion (.20%) had a toddler (age, 13–36 months) at home, who could potentially serve as a vector for acquisition of CMV in at least some instances of primary infection. Vaccine (20 micrograms of gB admixed with MF59 adjuvant) or placebo was administered according to a 0-, 1-, and 6-month schedule [19]. The primary endpoint reported in this study was the time to primary CMV infection, documented by seroconversion to non-gB CMV antigens, using an IgG assay from which the gB-specific antibodies had been removed [20]. An overall efficacy of 50% (95% confidence interval, 7%–73%) for prevention of CMV infection was observed. This exciting result suggested that a gB vaccine may be able to prevent primary infection and, by definition, congenital CMV transmission in young women. Given the encouraging results observed in this phase II study, is a solution Received 18 February 2011; accepted 22 February 2011. Potential conflicts of interest: M. R. S. has received funding from GSK to study preclinical models of CMV vaccines and has served as a consultant to Merck on the topic of CMV vaccines. Correspondence: Mark R. Schleiss, MD, Center for Infectious Diseases and Microbiology Translational Research, Div of Pediatric Infectious Diseases, Dept of Pediatrics, University of Minnesota Medical School, 2001 6th St SE, Minneapolis, MN, 55455 (schleiss@umn.edu). The Journal of Infectious Diseases 2011;203:1513–6 The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals. permissions@oup.com 0022-1899 (print)/1537-6613 (online)/2011/20311-0003$14.00 DOI: 10.1093/infdis/jir144
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