Breakthroughs on the Road Toward a CMV Vaccine

January 20, 2017 | by Letisia Marquez

breakthroughs - CMV scientists Felix Wussow, an assistant professor in City of Hope's Department of Experimental Therapeutics, and Flavia Chiuppesi, a staff scientist in the department.

Most babies born with congenital cytomegalovirus (CMV) don’t show any signs or symptoms. But for those who do, the symptoms can be severe, ranging from hearing and vision loss to intellectual disability to small head size and frequent seizures.

About one out of every 150 babies are born with congenital CMV infection, according to the Centers for Disease Control and Prevention. A recent New York Times report estimated that between 20,000 and 40,000 babies are born with CMV each year. Up to 8,000 of those have or develop permanent disabilities.

A recent study in the journal Blood also links congenital CMV infection to the development of acute lymphoblastic leukemia (ALL), the most common malignancy diagnosed in children. 

Currently, there is no vaccine to prevent CMV. But a team led by City of Hope’s Flavia Chiuppesi, a staff scientist with the Department of Experimental Therapeutics within Beckman Research Institute of City of Hope, and Felix Wussow, an assistant professor in the same unit, have devoted several years trying to finding a congenital CMV vaccine.

“Many people are already infected with CMV, but if you’re not  and you get infected during pregnancy, that’s the most risky situation for the fetus,” Chiuppesi said. “The mother has no protection at all and the virus can be easily transmitted to the fetus.”

A vaccine could be used to immunize the entire population against CMV, and thus prevent further transmission of the virus, Wussow said. In the United States, nearly one in three children are already infected with CMV by age 5. By the age of 40, over half of adults have been infected with CMV, according to the CDC.

The team’s vaccine strategy involves a virus called modified vaccinia Ankara, or MVA, that contains five key genes from CMV. The five genes carry the plans for producing a protein complex called the pentamer complex, which consists of five proteins found on the surface of CMV.

In their latest research, which published recently in the Journal of Virology, the team discovered the first antibody target site on the pentamer complex that could play an important role in preventing the transfer of the virus to the unborn child.

Chiuppesi explained that many viruses do not cross a mother’s placenta, though CMV does. Antibodies targeting the CMV pentamer complex could prevent this transmission from occuring.

With that discovery, the team is one step closer to their overall goal – developing a vaccine that can be tested in people, Wussow said.

“For 40 years, researchers have been working on this elusive vaccine, but our hope is that we are only a few years away from developing one for clinical use,” he added.

Additional City of Hope authors of the Journal of Virology study include City of Hope’s Department of Experimental Therapeutics’ Teodora Kaltcheva, a staff scientist; Meng Zhuo, a research associate; and Don J. Diamond, Ph.D., the department’s professor and chair. Peter A. Barry, vice-chair of research and professor at the Center for Comparative Medicine, University of California, Davis, also collaborated in this work.

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