Passive Immunization against Congenital Cytomegalovirus Infection: Current State of Knowledge

Abstract

Primary infection with the human cytomegalovirus (CMV) occurs in 1-4% of pregnancies. The rates of maternal-fetal CMV transmissions are around 25, 36, 41, and 66%, for infections occurring in the peri-conceptional weeks, first, second, and third trimester of pregnancy, respectively. On the other hand, the severity of fetal organ damage and dysfunction diminishes with increasing gestational age. Congenitally CMV-infected newborns may have neurosensory impairments like mental retardation, cerebral palsy, epilepsy, progressive hearing loss or visual defects, or even may have a fatal outcome. In in-vitro experiments, CMV specific neutralizing IgG antibodies - which are abundant in CMV specific hyperimmune globulin (HIG) products - inhibited the entry of the virus into target cells and hampered viral cell-to-cell spread. This article provides a brief overview on the epidemiology and diagnostic tools in congenital CMV infection. It also concisely summarizes the currently available study results on the safety and effectiveness of HIG treatment. Accordingly, in clinical studies HIG administration to expectant mothers following primary CMV infection (prophylactic use) was shown to lower the risk of maternal-fetal transmission of CMV compared to untreated controls. HIG was also able to ameliorate the disease sequelae in evidently infected fetuses (therapeutic use), as demonstrated by the regression or even resolution of sonographic pathologies including placental inflammation.

Evaluation of Pregnant Women Susceptible to Cytomegalovirus Infection in Maiduguri, Nigeria

“…This result agrees with the report that blood transfusion was shown to be a risk factor for transmission of CMV infection (Matos et al, 2010). This is true because CMV testing is not part of laboratory screening in blood transfusion services, coupled with the high IgM seropositivity in African societies, recipients are either endangered with contracting CMV infections or acquire passive immunity from IgG seropositive donors (Juckstock et al, 2015).…”

Highly efficient maternal-fetal Zika virus transmission in pregnant rhesus macaques

“…Modest fetal neurodevelopmental outcomes with the model we have described in this current report may provide an opportunity to further evaluate factors which foster severe fetal developmental impact, such as co-infection or previous exposure to other pathogens, and support the development of strategies to prevent maternal-fetal transmission and reduce fetal virus burden. Further information on the ontogeny of fetal infection and distribution of virus in the fetus during gestation using relevant animal models will be important to establish before consideration of interventional strategies, such as maternal or fetal passive immunization [51] in pregnant women presenting with symptoms of ZIKV infection.…”

Histological Analysis of Term Placentas from Hyperimmune Globulin-Treated and Untreated Mothers with Primary Cytomegalovirus Infection

“…In 2013, Nigro and Adler [6] reported both antiviral and immunomodulatory activities, which are crucial in regulating the innate and adaptive immune responses in the interplay between infection control and immunopathological processes. Studies on murine brains suggested that antibody treatment could mitigate inflammatory tissue damage and CMV replication [7, 8]. Furthermore, a study performed on a small group of human placentas showed that HIG can suppress CMV replication and induce compensatory mechanisms to prevent placental hypoxia, thus improving fetal outcome [9].…”