An exciting new vaccine strategy was recently announced by Director Peter Barry and colleagues at City of Hope that has the potential to prevent a viral infection that causes 5,000 babies yearly to be born with congenital neurological deficits.
Human cytomegalovirus, or HCMV, is a common virus, infecting from 50-100% of adults in different countries around the world. The virus is often contracted through contact with saliva or urine from HCMV-infected children – and commonly spread at preschools. Most HCMV infections are “silent,” with the majority of infected people showing no signs or symptoms. However, when HCMV is transmitted to pregnant women, usually from infected children shedding HCMV in bodily fluids, the infected mother can then transmit the virus to their fetus. HCMV infection in the fetus can result in permanent hearing loss, seizures and lifelong neurological deficits. 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.
Peter Barry, Ph.D., Core Scientist and director of the California National Primate Research Center (CNPRC), in collaboration with physicians from the City of Hope, conducted a study using a new vaccine strategy that shows great potential to induce antibodies that successfully fight the virus. The study was part of an NIH-funded project to Dr. Barry and 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, and was published in PLOS Pathogens on November 20, 2014 (Wussow F, et al. Human Cytomegalovirus Vaccine Based on the Envelope gH/gL Pentamer Complex. PLoS Pathog. 2014 Nov 20;10(11):e1004524).
“The synergy between the CNPRC and the City of Hope was possible only because of the nonhuman primate model at the CNPRC, and the work has high likelihood for direct translation to human clinical trials. This study clearly demonstrates that the vector system induces robust antibody responses in the clinically relevant rhesus macaque model, and the magnitude of the responses was so great in the macaques that we now have very high confidence in moving forward to studies in humans.” said Dr. Barry.
One pathway HCMV uses to enter cells and cause infection requires a viral protein complex made up of five individual viral proteins. This pentameric protein complex is essential to transmit the virus from an infected to an uninfected person, or from mother to fetus. Researchers constructed a vaccine that forms the viral pentamer using an often-used vaccine delivery vehicle, referred to as Modified Vaccinia Ankara (MVA), a virus from the same family that acts as a vaccine against smallpox.
Rhesus macaques at the CNPRC were immunized with this MVA to generate antibodies against the HCMV pentamer complex. The study expands on preclinical work conducted at the CNPRC and provides crucial information that is leading to development of a human vaccine by testing its ability to stimulate appropriate immune responses in a relevant primate species.
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 HCMV is transmitted from person to person.
MVA is currently being used in 150 active clinical trials for a variety of conditions. In fact, at City of Hope, a vaccine using MVA is already in the clinic targeting another part of HCMV 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 HCMV – 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.”