Biology Reference
In-Depth Information
reasons for the failure to achieve the goal of a licensed HCMV vaccine are
complex, but several key problems stand out. First, the host immune correlates
of protective immunity are not yet clear. Secondly, the viral proteins that should
be included in a HCMV vaccine are uncertain. Third, clinical trials have largely
focused on immunocompromised patients, a population that may not be relevant to
the problem of protection of the fetus against congenital infection. Fourth, the ulti-
mate target population for HCMV vaccination remains unclear. Finally, and most
importantly, there has been insufficient education about the problem of HCMV
infection, particularly among women of child-bearing age and in the lay public.
This review considers the strategies that have been explored to date in development
of HCMV vaccines, and summarizes both active clinical trials as well as novel
technologies that merit future consideration toward the goal of prevention of this
significant public health problem.
Spectrum of HCMV Disease, Rationale for Vaccine,
and Target Population
Congenital HCMV Infection: A Major Public Health Problem
The problem of congenital HCMV infection is unquestionably the major driving
force behind efforts to develop a HCMV vaccine. In the developed world,
HCMV is the most common congenital viral infection (Whitley 1994). Estimates
of the prevalence of congenital HCMV infection suggest that between 0.5% and
2% of all newborns in the developed world are infected in utero (Demmler
1996). In the United States alone, this corresponds to approximately 40,000
infected newborn infants born annually with HCMV infection. The concern is
particularly acute for HCMV-seronegative women of child-bearing age. Based
on recent HCMV incidence estimates, approximately 27,000 new infections are
believed to occur among seronegative pregnant women in the United States each
year (Colugnati et al. 2007). Approximately 10% of congenitally infected
infants have clinically evident disease in the newborn period, including visceral
organomegaly, microcephaly with intracranial calcifications, chorioretinitis, and
skin lesions including petechiae and purpura. Although the majority of congeni-
tally infected infants appear normal at birth, these children are nonetheless at
risk for neurodevelopmental sequelae, in particular sensorineural hearing loss
(SNHL). Antiviral therapy in infected newborns with neurologic involvement is
of value in ameliorating the severity and progression of SNHL (Kimberlin et al.
2003), but the toxicities of available antiviral agents are of concern, and the
benefits of therapy are limited. Therefore, there are few medical interventions
currently available to prevent or limit HCMV-induced neurological morbidity in
infants, underscoring the urgent need for vaccine development.
