Weill Cornell Medicine was awarded a $4.2 million Program Project Grant renewal from the National Institutes of Health’s (NIH) National Institute of Allergy and Infectious Diseases (NIAID). This will fund the development of a vaccine that can prevent the cytomegalovirus (CMV) from being transmitted from mother to baby during pregnancy—the most common congenital infection worldwide.
The prestigious Program Project Grant has the possibility to be extended for a total of five years and $20.4 million to support collaborative, multi-project research toward effective information sharing and research synergy that may speed the path to a vaccine.
Several companies, like Moderna and Merck, are testing vaccines for their ability to protect pregnant women from CMV infection, thereby reducing the chances of transmission to the fetus. However, Dr. Sallie Permar, the chair of the Department of Pediatrics at Weill Cornell Medicine, is leading the program to test vaccine approaches that will prevent transmission of the virus to protect the developing fetus.
Worldwide, about one in 200 babies is born with CMV and one-quarter of them experience long-lasting impairments, including hearing loss, smaller than average head size (microcephaly), developmental delays and seizures.
“CMV causes fetal birth defects and brain damage much like what was recognized in the Zika epidemic, except it affects ten times as many infants and it happens every year across the globe,” Dr. Permar said. “If we could eliminate this terrible congenital infection, we would give more babies the chance to achieve their full potential in life.”
Modeling Maternal CMV Transmission
More than half of all adults live with CMV a common type of herpes virus; however, if a woman acquires CMV for the first-time during pregnancy, she has a 30 to 40 percent chance of passing the virus along to her baby.
Designing a clinical trial large enough to assess the effectiveness of a CMV vaccine to protect the fetus is challenging. To overcome that issue, Dr. Permar has worked with collaborators at the University of California Davis Primate Center, Tulane University and Oregon Health Sciences University (OSHU) and Primate Center to develop a non-human primate model of congenital CMV transmission where vaccines can be tested for their ability to prevent virus transmission to the fetus. “This work requires a cadre of multidisciplinary virologists, immunologists, pathologists, physicians and veterinary scientists who all care deeply about eliminating this devastating childhood infection through vaccination,” Dr. Permar said.
In the original project grant, the team used this model to determine which maternal immune responses helped prevent transmission and to explore the mechanisms the virus uses to avoid detection and clearance from the immune system. “CMV has evolved multiple strategies for evading host immunity,” Dr. Permar said. The virus hides inside a person’s cells, where it produces factors that capture host antibodies, disables common killer T cells and generally misdirects and confuses the antiviral immune response.
Disarming CMV’s Immune-Evading Tactics
Now, in the grant renewal, the researchers will test different approaches for thwarting these viral immune-evading tactics. They will deploy weakened viruses unable to cause disease but still capable of eliciting a less common type of T cell against which CMV has no molecular defenses. They will also use some of the virus’s own protein factors as antigens to induce the production of antibodies that can counteract CMV’s evasive maneuvers.
Within five years, the researchers envision having a prototype for a CMV vaccine that protects against congenital infection. They could then make recommendations to industry about the components that could be added to CMV vaccines currently being tested in clinical trials to prevent fetal infection.
Many Weill Cornell Medicine physicians and scientists maintain relationships and collaborate with external organizations to foster scientific innovation and provide expert guidance. The institution makes these disclosures public to ensure transparency. For this information, please see the profile for Dr. Sallie Permar.
This research was supported by the NIAID under Award Number P01AI129859. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.