A neutralizing anti-gH/gL monoclonal antibody is protective in the guinea pig model of congenital CMV infection.

Marcy R Auerbach,Y Gloria Meng,Samantha Lein,Becket Feierbach,Jean-Michel Vernes,Donghong Yan,Nicholas Lewin-Koh,Rajesh Vij,Gerald Nakamura,Jed Ross,Pamela Chan,Min Xu,Richard Carano,Jo-Anne Hongo,Rong Deng,Peter A Barry

doi:10.1371/journal.ppat.1004060

Abstract

Human cytomegalovirus (HCMV) is the most common cause of congenital virus infection. Congenital HCMV infection occurs in 0.2–1% of all births, and causes birth defects and developmental abnormalities, including sensorineural hearing loss and developmental delay. Several key studies have established the guinea pig as a tractable model for the study of congenital HCMV infection and have shown that polyclonal antibodies can be protective [1]–[3]. In this study, we demonstrate that an anti-guinea pig CMV (GPCMV) glycoprotein H/glycoprotein L neutralizing monoclonal antibody protects against fetal infection and loss in the guinea pig. Furthermore, we have delineated the kinetics of GPCMV congenital infection, from maternal infection (salivary glands, seroconversion, placenta) to fetal infection (fetus and amniotic fluid). Our studies support the hypothesis that a neutralizing monoclonal antibody targeting an envelope GPCMV glycoprotein can protect the fetus from infection and may shed light on the therapeutic intervention of HCMV congenital infection in humans.

Highlights

Human cytomegalovirus (HCMV), a member of the herpesvirus family, is widely distributed in the human population and can cause severe disease in immunocompromised patients and upon infection of the fetus
We have delineated the kinetics of maternal to fetal infection and found that congenital infection is rapid following maternal infection
Our studies may be informative for development of a therapeutic intervention to treat congenital HCMV infection in humans

Summary

Introduction

Human cytomegalovirus (HCMV), a member of the herpesvirus family, is widely distributed in the human population and can cause severe disease in immunocompromised patients and upon infection of the fetus. Several lines of evidence suggest that neutralizing antibodies can protect the fetus from HCMV infection and disease. Preconception maternal antibodies to HCMV significantly reduce the severity and risk of congenital HCMV infection in future pregnancies, the frequency of sensorineural deafness is the same [6,8]. Early appearance of maternal antibodies against the HCMV glycoprotein entry complex, gH/gL/UL128/UL130/UL131, correlates with a lack of vertical transmission, suggesting that antibodies against this complex can effectively neutralize the virus in vivo [9,10]. A small, open-label study showed that hyperimmuneglobulin could protect the fetus from HCMV infection and disease [11].

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