City of Hope study: Vaccine effective against virus responsible for 5,000 congenital infections annually
November 19, 2014

Laboratory models show vaccine has potential to prevent congenital cytomegalovirus infection
 
DUARTE, Calif. A new vaccine strategy can potentially prevent a viral infection that causes 5,000 babies yearly to be born with permanent disabilities.

Cytomegalovirus, or CMV, is a common virus, often contracted through contact with saliva or urine from children – and commonly spreads at preschools. Most CMV infections are “silent,” with the majority of people infected showing no signs or symptoms. However, when pregnant women transmit the virus to their fetus, the congenital infection can result in permanent hearing loss, seizures and developmental disabilities. 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.

A City of Hope laboratory study using two different models with a new vaccine strategy shows great potential to induce antibodies that successfully fight the virus. The study was published in PLOS Pathogens on November 20.
“The vector system we studied is often already used in human patients for a variety of conditions, and our findings indicate that it induces unbelievably potent antibodies that could neutralize CMV infection,” said Don J. Diamond, Ph.D., associate chair of the Department of Virology, director of Translational Vaccine Research at City of Hope and senior author of the study. “With this new data, we’re at the point where we feel very confident this vaccine is ready for clinical evaluation.” Felix Wussow, Ph.D., and Flavia Chiuppesi, Ph.D., in the Division of Translational Vaccine Research, were the lead authors of the study at City of Hope.

One pathway CMV uses to enter cells and cause infection requires a viral protein made up of five parts. This complex is referred to as a pentamer and is necessary to pass the virus from person to person or from mother to fetus. Researchers here constructed a vaccine that forms the viral pentamer using an often used vaccine delivery vehicle referred to as Modified Vaccinia Ankara, a virus from the same family that acts as a vaccine against small pox. Remarkably, the vaccine caused the formation of antibodies that could completely prevent viral infection of human placental cells even when diluted 200,000 times which highlights their potency. Researchers also found highly potent antibodies that were induced by the vaccine in the saliva and mucus – protecting the nose and mouth, which is how CMV is transmitted from person to person.

The vaccine delivery vehicle called MVA is currently being used in 150 active clinical trials for a variety of conditions. In fact, at City of Hope, two vaccines using MVA are already in the clinic. One targets solid tumors and the other targets another part of CMV that is important for transplant recipients, including patients receiving bone marrow or other hematopoietic cell transplants.

“It’s very promising that a vaccine we already know to be used in human patients at the City of Hope and across the world could have this new application,” Diamond said. “A vaccine capable of protecting against CMV – the leading viral cause of developmental disabilities – could also prove valuable to immune-compromised patients such as our hematologic malignancy transplant recipients, who are also vulnerable to this particular virus.”

Collaborators and cooperating institutions include Peter A. Barry, Ph.D., vice chair of research at the University of California at Davis, and Rana Chakraborty, M.D., Ph.D., director of the Ponce Family and Youth Clinic at Emory University Medical Center. Support for the research came from grants awarded by the National Institute of Allergy and Infectious Diseases (NIAID).
 
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About City of Hope
City of Hope is a leading research and treatment center for cancer, diabetes and other life-threatening diseases. Designated as a comprehensive cancer center, the highest recognition bestowed by the National Cancer Institute, City of Hope is also a founding member of the National Comprehensive Cancer Network, with research and treatment protocols that advance care throughout the nation. City of Hope’s main hospital is located in Duarte, California, with clinics in Antelope Valley and South Pasadena and has been ranked as one of “America’s Best Hospital” in cancer by U.S. News & World Report. Founded in 1913, City of Hope is a pioneer in the fields of bone marrow transplantation and genetics.