A groundbreaking study co-authored by Weill Cornell Medicine and Oregon Health & Science University (OHSU) researchers has provided critical new insights into the development of a vaccine to prevent the transmission of cytomegalovirus (CMV) from pregnant women to their fetuses. The study, published in Science Translational Medicine on March 12, offers valuable information that could help pave the way for more effective vaccines aimed at blocking CMV spread across the placenta.
CMV is one of the most prevalent viruses globally, yet most infected individuals remain unaware due to the virus’s often mild or asymptomatic nature. However, for pregnant women, the virus poses significant risks to their developing fetuses. CMV can cause lifelong health complications for babies, including hearing loss, developmental delays, and neurological impairments. In fact, CMV is the leading cause of congenital infections worldwide, with about 1 in 200 babies born in the U.S. contracting the virus. Unfortunately, up to 20% of these babies experience severe birth defects or long-term health issues.
Despite the virus’s widespread impact, no vaccine has been successfully developed to prevent the transmission of CMV from mother to fetus. Over the past four decades, clinical research has focused on understanding the interactions between the virus and the human host, particularly how CMV crosses the placenta and infects the fetus. Researchers believe that understanding these interactions is key to developing a vaccine capable of preventing transmission during pregnancy.
The recent study challenges some of the assumptions held by researchers in the field of CMV vaccine development. Historically, one of the key vaccine targets has been the CMV pentameric complex, a combination of proteins essential for CMV infection of specific cell types. It was widely believed that targeting this viral complex would block the virus’s ability to cross the placenta and infect the fetus.
However, the study’s findings suggest that CMV viruses lacking the pentameric complex were still able to cross the placenta and cause harm to the fetus. This surprising discovery indicates that other viral proteins may be involved in the placental transmission process and need to be included in future vaccine designs.
The study was conducted using non-human primate models, a more accurate representation of human CMV infection. Dr. Klaus Früh, Professor at OHSU Vaccine and Gene Therapy Institute, and Dr. Hsuan-Yuan (Sherry) Wang, a post-doctoral scholar in the group of Dr. Daniel Malouli, led the research. They hypothesized that neutralizing antibodies against the pentameric complex could prevent placental transmission. However, their results showed that CMV could still spread to the fetus even in the absence of this complex.
The team’s findings challenge the prevailing assumption that the pentameric complex is the sole target for preventing CMV transmission. The researchers stress that this indicates a need to explore additional viral proteins to ensure an effective vaccine design that blocks cross-placental transmission.
Senior author Dr. Daniel Malouli, Assistant Professor at OHSU’s Vaccine and Gene Therapy Institute, emphasized the importance of understanding virus-host interactions to develop a more effective vaccine. “More robust information on the interactions between the virus and the human host is crucial for the selection of promising targets that can be used for the development of an effective vaccine,” he said.
Dr. Sallie Permar, co-corresponding author and Chair of the Department of Pediatrics at Weill Cornell Medicine, expressed optimism about the study’s impact. “These findings are exciting because they bring us one step closer to the development of an effective vaccine, which we hope can protect pregnant women and babies around the world,” she stated.
While this study does not immediately offer a definitive solution, it provides a crucial step forward in understanding how CMV can cross the placenta and cause fetal harm. The research team is committed to continuing their work to identify additional viral proteins that could serve as vaccine targets. By refining our understanding of the virus’s behavior, the hope is that an effective vaccine will eventually be developed and widely distributed, offering a much-needed solution for preventing congenital CMV infections and the associated long-term health issues for babies.
The continued collaboration between institutions like Weill Cornell Medicine and OHSU is vital in advancing CMV research, bringing us closer to developing the necessary tools to protect vulnerable populations, particularly pregnant women and their unborn children, from the silent threat of CMV.
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