Mother-to-infant transmission of high-risk infection: new monkey model

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Mother-to-infant transmission of high-risk infection: new monkey model

Dr. Peter Barry’s innovative research program using the rhesus monkey as a model of CMV infection leads to a successful study in placental transmission

Cytomegalovirus (CMV) infection is highly prevalent in humans, infecting from 50-100% of adults around the world. The virus is often contracted through contact with saliva or urine from CMV-infected children – and commonly spread at preschools.

Most CMV infections are “silent,” with the majority of infected people showing no signs or symptoms. However, when CMV is transmitted to pregnant women, usually from infected children shedding CMV in bodily fluids, the infected mother can then transmit the virus to their fetus through the placenta. Congenital CMV is the leading infectious cause of childhood hearing loss and brain damage worldwide, which is why it is often referred to as the “birth defect virus”. A vaccine that works against the virus is a top priority of the Institute of Medicine because of the potential to save lives and prevent disabilities in children.

Knowledge of the infection process is critical to the design of effective CMV vaccines. A recent study by a large team of investigators from multiple institutions including the California National Primate Research Center (CNPRC) at UC Davis, reported the development of a new rhesus monkey model for CMV placental transmission. The study was led by Kristy Bialas, PhD (Duke Human Vaccine Institute) with collaborators from Tulane, New England and Wisconsin National Primate Research Centers, the Boston Children’s Hospital and the City of Hope. Providing insight into the mechanism of protection against congenital transmission following maternal CMV infection, Dr. Bialas and her colleagues revealed an association between delayed maternal antibody responses and severe fetal outcome.

Central to the successful completion of the study was the participation of Peter Barry, PhD, CNPRC Core Scientist and director of the Center of Comparative Medicine at UC Davis.  Dr. Barry has been studying CMV in rhesus macaques for over 30 years. He began his research at the Primate Center as a graduate student and received guidance from Preston Marx, PhD (then a CNPRC Core Scientist) who advised him on how he might be able to isolate rhesus CMV (RhCMV). Dr. Barry’s graduate school research, along with past work conducted with collaborator Alice Tarantal, PhD (CNPRC Reproductive Sciences and Regenerative Medicine Unit Core Scientist), led to the development of a unique nonhuman primate model of intrauterine RhCMV disease.

As a result of Dr. Barry’s innovative research program using the rhesus monkey as a model of CMV infection, clinical-like isolates of RhCMV from the CNPRC made it possible for a multi-institutional collaborations with investigators from across the country to successfully establish placental transmission of CMV in a nonhuman primate. It is anticipated that the new nonhuman primate model of CMV placental transmission will further inform human vaccine strategies and treatment of congenital CMV infections.   Most recently, Dr. Barry reported the pre-clinical testing of a vaccine against CMV in rhesus monkeys, lending support to the idea that congenital infections might be prevented in the near future (November 2014, CNPRC News 12-1-14).

The CNPRC is one of seven National Primate Research Centers (NPRC) supported by the National Institutes of Health. This research was conducted in collaboration with the Tulane, New England, and Wisconsin National Primate Research Centers. The research was funded by National Institutes of Health (NIH) Office of the Director, NIH National Cancer Institute, NIH National Institute of Allergy and Infectious Diseases, NIH Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the Derfner Children’s Miracle Network Research Grant.

Bialasa KM, et al. Maternal CD4+ T cells protect against severe congenital cytomegalovirus disease in a novel nonhuman primate model of placental cytomegalovirus transmission.  Proc Nat Acad Sci, 10-15-15

The New York Times, October 19, 2015
Serious Human In Utero Infection Is Found in Rhesus Monkeys

Science Daily, October 19, 2015
http://www.sciencedaily.com/releases/2015/10/151019154717.htm