Biology Reference
In-Depth Information
preconception immunity, only infants born in the primary-infection group had
symptomatic disease at birth. These infants were at the highest risk for long-term
sequelae (Fowler et al. 1992). However, a recent study suggests that preconceptual
immunity does not completely eliminate the risk of symptomatic congenital trans-
mission. In this study, some women who were seropositive for HCMV were none-
theless susceptible to reinfection with a new HCMV strain during pregnancy, and
such reinfections did lead in some cases to symptomatic disease in the neonate
(Boppana et al. 2001). In light of these data, a HCMV vaccine may not completely
eliminate the potential for congenital HCMV transmission. Substantial evidence
nonetheless strongly suggests that a HCMV vaccine program would protect many
newborns. Other lines of evidence indicate that preconceptual immunity reduces
both the incidence of congenital transmission and the severity of disease if trans-
mission occurs. In a recent study that followed over 3,000 women from one preg-
nancy to the subsequent pregnancy and delivery, the rate of congenital HCMV
infection was three times higher in offspring of women who initially were HCMV
seronegative (Fowler et al. 2003). Preconception immunity was clearly protective
in this study and resulted in a 69% reduction of congenital HCMV infection.
Protection against congenital HCMV infection is enhanced by longer time intervals
between pregnancies (Fowler et al. 2004). This effect is likely due to maturation of
antibody avidity against HCMV (Revello and Gerna 2002). Therefore, emphasis
should be placed on developing HCMV vaccines that are capable of mimicking the
protective components of natural immunity, particularly antibody avidity, and such
vaccines would likely have a significant impact on preventing symptomatic con-
genital HCMV infections.
Lessons from Adoptive Transfer Studies
Additional evidence supporting the protective role of immunity in preventing symp-
tomatic congenital HCMV transmission comes from recently described passive
immunization studies, using high-titer anti-HCMV immunoglobulin. In this study
(Nigro et al. 2005), pregnant women with a primary HCMV infection were offered
intravenous HCMV hyperimmune globulin, in two different dose regimens (therapy
and prevention groups). In the therapy group, only 1 of 31 women gave birth to an
infant with HCMV disease (defined as an infant who was symptomatic at birth and
handicapped at 2 or more years of age), compared with 7 of 14 women in an
untreated control group. In the prevention group, 6 of 37 women who received
hyperimmune globulin during pregnancy had infants with congenital HCMV
infection, compared with 19 of 47 women who did not receive the high-titer HCMV
globulin. Although uncontrolled, these data support the protective effect of humoral
immunity in prevention of fetal HCMV-associated disease. Additional randomized
controlled trials of immune globulin are warranted in high-risk pregnancies, to
further validate the protective effect of passive immunization.
