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9/26/2014  |   10:00 AM - 10:30 AM   |  Ballroom B

A Nonhuman Primate Model for the Treatment of Congenital CMV Infection

Human cytomegalovirus (HCMV) will remain a significant congenital threat to fetuses/newborns in the absence of protective prevention and/or therapeutic strategies. Passive immunization of CMV hyperimmune globulin (HIG) has been proposed as a potential prophylactic and therapeutic treatment in the prevention of congenital HCMV infection and disease. Its potential efficacy has shown promise in unblinded, non-randomized, and non-placebo controlled trial, but these early results have not confirmed in a large, well-designed randomized trial. Given the fact that discrepant efficacy can result from different diagnostic criteria, treatment regimens, immune globulin preparations, and the potential difficulties related to human studies, it is important to have a relevant model for congenital HCMV infection and treatment. Our previous studies have demonstrated that rhesus CMV (RhCMV) infection of rhesus macaques represents a relevant nonhuman primate (NHP) model to understand intrauterine pathogenesis by HCMV, which, in turn, indicates its potential being a model to evaluate the treatment effect of HCMV HIG against congenital HCMV disease. As a first step to this aim, we compared the virulence of two RhCMV strains – laboratory strain 68-1 and wild-type strain UCD59 in experimentally inoculated fetuses of RhCMV-infected dams. Four groups of fetuses were inoculated intraperitoneally with two different titers of either UCD59 or 68-1. Significantly lower survival rates were observed in fetuses that were inoculated with higher titers of UCD59, and reduced rates of survival in fetuses inoculated with the higher titer of 68-1. Since these studies were conducted in fetuses of dams with prior immunity to RhCMV, the results suggest that maternal antiviral IgG in fetal circulation may have provided limited protection against the pathogenic outcomes following the lower titers of inoculation. This study demonstrates that the NHP model can be used to rigorously evaluate the optimal strategy of therapeutic HIG treatment of congenitally infected fetuses.

Yujuan Yue (Primary Presenter), yyue@ucdavis.edu;
Yujuan Yue is a virology specialist in the Center of Comparative Medicine at UC, Davis. She received her MD in 1986 from the medical school of Qingdao University, China and Ph.D in 2004 from the deparment of comparative pathology at UC, Davis. She has been working on a model of rhesus cytomegalovirus (RhCMV) to investigate HCMV pathogenesis, preventive and therapeutic strategies since her graduate study. Working together with Dr. Peter Barry and members in his laboratory, they have demonstrated RhCMV infection of rhesus macaques recapitulates HCMV infection of humans and represents a relevant nonhuman primate model for HCMV .

ASHA DISCLOSURE:

Financial - No relevant financial relationship exist.

Nonfinancial - No relevant nonfinancial relationship exist.

Peter Barry (Author), pabarry@ucdavis.edu;
Peter A. Barry received a bachelor's degree in Molecular, Cellular, and Developmental Biology in 1976 from the University of Colorado and completed his doctorate in the laboratory of Dr. Mario Capecchi at the University of Utah. He finished his postdoctoral training in the Department of Pathology, UC Davis and became a Core Faculty Member of the Center for Comparative Medicine in 1998. Currently, he holds an appointment as a professor and director of CCM. Dr.Barry’s laboratory focuses on infection of rhesus macaques with rhesus cytomegalovirus (RhCMV) as an in vivo system to studies human CMV (HCMV). Their studies have shown the relevance of the rhesus macaque model to investigate viral mechanisms of HCMV persistence and pathogenesis, and to evaluate prevention and intervention strategies that can limit infection and/or prevent viral disease.

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340YujuanYue.pdf

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