A neutralizing anti-gH/gL monoclonal antibody is protective in the guinea pig model of congenital CMV infection.
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. 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.
Department of Infectious Diseases, Genentech, South San Francisco, California, United States of America.
Marcy R
MR
Auerbach
Department of Translational Immunology, Genentech, South San Francisco, California, United States of America.
Donghong
D
Yan
Department of Antibody Engineering, Genentech, South San Francisco, California, United States of America.
Rajesh
R
Vij
Department of Antibody Engineering, Genentech, South San Francisco, California, United States of America.
Jo-Anne
JA
Hongo
Department of Antibody Engineering, Genentech, South San Francisco, California, United States of America.
Gerald
G
Nakamura
Department of Biochemical and Cellular Pharmacology, Genentech, South San Francisco, California, United States of America.
Jean-Michel
JM
Vernes
Department of Biochemical and Cellular Pharmacology, Genentech, South San Francisco, California, United States of America.
Y Gloria
YG
Meng
Department of Antibody Engineering, Genentech, South San Francisco, California, United States of America.
Samantha
S
Lein
Department of Biochemical and Cellular Pharmacology, Genentech, South San Francisco, California, United States of America.
Pamela
P
Chan
Department of Biomedical Imaging, Genentech, South San Francisco, California, United States of America.
Jed
J
Ross
Department of Biomedical Imaging, Genentech, South San Francisco, California, United States of America.
Richard
R
Carano
Department of Clinical Pharmacology, Genentech, South San Francisco, California, United States of America.
Rong
R
Deng
Department of Biostatistics, Genentech, South San Francisco, California, United States of America.
Nicholas
N
Lewin-Koh
Department of Translational Immunology, Genentech, South San Francisco, California, United States of America.
Min
M
Xu
Department of Infectious Diseases, Genentech, South San Francisco, California, United States of America.
Becket
B
Feierbach
D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000276:immunology / Q000494:pharmacology*; D057134:Antibodies, Neutralizing / Q000276:immunology / Q000494:pharmacology*; D000914:Antibodies, Viral / Q000276:immunology / Q000494:pharmacology*; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000151:congenital* / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D006168:Guinea Pigs; D057809:HEK293 Cells; D006801:Humans
D058846:Antibodies, Monoclonal, Murine-Derived; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral