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

Auerbach, Marcy R.; Yan, Donghong; Vij, Rajesh; Hongo, Jo-Anne; Nakamura, Gerald; Vernes, Jean-Michel; Meng, Y. Gloria; Lein, Samantha; Chan, Pamela; Ross, Jed; Carano, Richard; Deng, Rong; Lewin-Koh, Nicholas; Xu, Min; Feierbach, Becket
April 2014
PLoS Pathogens;Apr2014, Vol. 10 Issue 4, p1
Academic Journal
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.


Related Articles

  • Identification by Mass Spectrometry and Immune Response Analysis of Guinea Pig Cytomegalovirus (GPCMV) Pentameric Complex Proteins GP129, 131 and 133. Gnanandarajah, Josephine S.; Gillis, Peter A.; Hernandez-Alvarado, Nelmary; LeeAnn Higgins; Markowski, Todd W.; Heungsup Sung; Lumley, Sheila; Schleiss, Mark R. // Viruses (1999-4915);Feb2014, Vol. 6 Issue 2, p727 

    Development of a vaccine against congenital infection with human cytomegalovirus (HCMV) is a major public health priority. A potential vaccine target receiving considerable recent attention is the pentameric complex (PC) of HCMV proteins consisting of gL, gH, UL128, UL130, and UL131, since some...

  • Effect of Maternal Treatment with Cyclic HPMPC in the Guinea Pig Model of Congenital Cytomegalovirus Infection. Bravo, Fernando J.; Cardin, Rhonda D.; Bernstein, David I. // Journal of Infectious Diseases;2/15/2006, Vol. 193 Issue 4, p591 

    Background. Cytomegalovirus (CMV) infection of the fetus is the leading cause of congenital infection. Using the guinea pig model of congenital CMV infection, we sought to determine whether antiviral treatment of a CMV- infected dam could improve the outcome of offspring. Methods. Pregnant...

  • Preconceptual Administration of an Alphavirus Replicon UL83 (pp65 Homolog) Vaccine Induces Humoral and Cellular Immunity and Improves Pregnancy Outcome in the Guinea Pig Model of Congenital Cytomegalovirus Infection. Schleiss, Mark R.; Lacayo, Juan C.; Belkaid, Yasmine; McGregor, Alistair; Stroup, Greg; Rayner, Jon; Alterson, Kimberly; Chulay, Jeffrey D.; Smith, Jonathan F. // Journal of Infectious Diseases;3/15/2007, Vol. 195 Issue 6, p789 

    Development of a vaccine against congenital cytomegalovirus (CMV) infection is a major public health priority. We report the use of a propagation-defective, single-cycle, RNA replicon vector system, derived from an attenuated strain of the alphavirus Venezuelan equine encephalitis virus, to...

  • A guinea pig model for cytomegalovirus congenital infection: dose-effect and vertical transmission rate. Benoist, Guillaume; Ville, Yves; Rouzioux, Christine; Delezoide, Anne-Lise; Flori, Pierre; Leruez-Ville, Mariane // Retrovirology;2008 Supplement 1, Vol. 5, Special section p1 

    Backgrounds and objectives Animal models are necessary to test new antiviral drugs to prevent CMV materno foetal transmission. Among the small animal CMV models, the guinea pig CMV (GPCMV) has the ability to cross the placenta, causing disease in utero. The objective was to study the relation...

  • Genetically engineered live-attenuated cytomegalovirus (CMV) vaccines improve pregnancy outcome in the guinea-pig model of congenital CMV infection. Schleiss, Mark R.; McGregor, Alistair; Yeon Choi; Anderson, Jodi; Leviton, Mike; Xiaohong Cui; McVoy, Michael // Retrovirology;2008 Supplement 1, Vol. 5, Special section p1 

    Background Congenital CMV infection is a major cause of disability in newborns. An effective preconception vaccine is a major public health priority. The guinea-pig cytomegalovirus (GPCMV) model was utilized to evaluate the efficacy of live, attenuated CMV vaccines generated using a bacterial...

  • Growth of Listeria monocytogenes in the Guinea Pig Placenta and Role of Cell-to-Cell Spread in Fetal Infection. Bakardjiev, Anna I.; Stacy, Brian A.; Portnoy, Daniel A. // Journal of Infectious Diseases;6/1/2005, Vol. 191 Issue 11, p1889 

    Listeria monocytogenes causes foodborne outbreaks that lead to infection in human and other mammalian fetuses. To elucidate the molecular and cellular mechanisms involved in transplacental transmission, we characterized placental-fetal infection in pregnant guinea pigs inoculated with wild-type...

  • Molecular and Biological Characterization of a New Isolate of Guinea Pig Cytomegalovirus. Schleiss, Mark R.; McAllister, Shane; Armién, Anibal G.; Hernandez-Alvarado, Nelmary; Fernández-Alarcón, Claudia; Zabeli, Jason C.; Ramaraj, Thiruvarangan; Crow, John A.; McVoy, Michael A. // Viruses (1999-4915);Feb2014, Vol. 6 Issue 2, p448 

    Development of a vaccine against congenital infection with human cytomegalovirus is complicated by the issue of re-infection, with subsequent vertical transmission, in women with pre-conception immunity to the virus. The study of experimental therapeutic prevention of re-infection would ideally...

  • PIII-79. Couture, L.; Nash, J. A.; Nguyen, L.; Turgeon, J. // Clinical Pharmacology & Therapeutics;Feb2006, Vol. 79 Issue 2, pP80 

    Background: P-glycoprotein (P-gp), an ABC transporter, is expressed in normal tissues such as the heart. Domperidone, a P-gp substrate, is associated with a block of voltage-gated cardiac K+ channels and drug-induced Long QT syndrome. The aim of our study was to determine effects of verapamil...

  • Structural Analogues Inhibit the Sensitizing Capacity of Carvone. Karlberg, Ann-Therese; Nilsson, Anna-Malin; Luthman, Kristina; Nilsson, J. Lars G. // Acta Dermato-Venereologica;Nov/Dec2001, Vol. 81 Issue 6, p398 

    The aim of the study was to investigate the effect of non-allergenic structural analogues on the sensitizing potential of carvone, a fragrance allergen. The possibility that one molecule might inhibit the allergenic activity of another molecule has been debated for 25 years. The Research...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics