A Neutralizing Anti-gH/gL Monoclonal Antibody Is Protective in the Guinea Pig Model of Congenital CMV Infection

PLoS Pathogens

Gerald Nakamura¹  Jo-Anne Hongo¹  Rajesh Vij¹  Samantha Lein¹  Y. Gloria Meng²  Pamela Chan²  Jean-Michel Vernes²  Jed Ross³  Richard Carano³  Nicholas Lewin-Koh⁴  Rong Deng⁵  Marcy R. Auerbach⁶  Becket Feierbach⁶  Donghong Yan⁷  Min Xu⁷ 

[1] Department of Antibody Engineering, Genentech, South San Francisco, California, United States of America;Department of Biochemical and Cellular Pharmacology, Genentech, South San Francisco, California, United States of America;Department of Biomedical Imaging, Genentech, South San Francisco, California, United States of America;Department of Biostatistics, Genentech, South San Francisco, California, United States of America;Department of Clinical Pharmacology, Genentech, South San Francisco, California, United States of America;Department of Infectious Diseases, Genentech, South San Francisco, California, United States of America;Department of Translational Immunology, Genentech, South San Francisco, California, United States of America

关键词: Guinea pigs;    Antibodies;    Monoclonal antibodies;    Cytomegalovirus infection;    Polymerase chain reaction;    Placenta;    Enzyme-linked immunoassays;    Salivary gl;    s;   

DOI  :  10.1371/journal.ppat.1004060

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY