The March towards a Vaccine for Congenital CMV: Rationale and Models

CMV is a ubiquitous human herpesvirus that causes a lifelong, persistent infection in its host. Whereas primary CMV infections in otherwise healthy individuals are typically asymptomatic and go unnoticed, complications can develop in immunosuppressed individuals following acute CMV infection or CMV reactivation, presenting as retinitis, hepatitis, pneumonitis, gastroenteritis, or other end-organ diseases [1]. Similar severe and life-threatening conditions can arise following CMV infection of the developing fetus, resulting in lasting neurologic deficits, and while not as well known as other common causes of pediatric disabilities, congenital CMV (cCMV) is the leading infectious cause of hearing loss and cognitive impairment in newborns worldwide [2]. The impact of cCMV infection on pediatric health is significant, affecting 0.5%–2% of all live-born infants worldwide [1]. In the United States, approximately 30,000 congenital infections occur annually, of which more than than 5,000 infections lead to permanent disabilities, including sensorineural hearing loss (SNHL), growth restriction, seizures, and motor and cognitive disability [1,2]. An estimated 10% of infected infants exhibit neurological sequelae at birth, while an additional 10%–15% of infected infants develop SNHL in the first two years of life, making CMV the leading nongenetic cause of childhood SNHL [1,2]. Much like the rubella vaccine effectively eliminated congenital rubella syndrome in the Americas, a maternal vaccine that elicits protective immune responses is needed to eliminate CMV as a major cause of birth defects.