Promising Results for Investigational mRNA Vaccine Against CMV

A recent study conducted by investigators at Weill Cornell Medicine has shown promising results for an mRNA vaccine against human cytomegalovirus (CMV), a virus that can cause birth defects when transmitted to babies during pregnancy.

The study, published in the Journal of Infectious Diseases, found that the mRNA-1647 vaccine candidate developed by Moderna elicited strong immune responses. The mRNA vaccine is now in phase 3 clinical trials to determine its effectiveness in protecting against CMV.

When a baby is born with CMV infection, it is called congenital CMV. Approximately one in 200 babies is born with congenital CMV and about one in five with congenital CMV will experience long-term health complications.

“Cytomegalovirus is the most common cause of congenital infection and the leading non-genetic cause of hearing loss in childhood,” Sallie Permar, M.D., Ph.D., senior author of the study and chair of the Department of Pediatrics at Weill Cornell Medicine told Managed Healthcare Executive in an interview.

She explained that while CMV does not cause serious illness in healthy adults, it can lead to birth defects and brain damage in babies infected during pregnancy, as well as life-threatening infections in individuals with compromised immune systems, such as organ transplant recipients.

Researchers have been working diligently to develop a CMV vaccine for more than 50 years. Permar explained that previous attempts have included various vaccine technologies. Nothing has resulted in a licensed product yet, she said, but progress has been made.

A previous vaccine candidate, gB/MF59, demonstrated partial success. Developed based on the viral surface protein, glycoprotein B, the vaccine was shown to be about 50% protective in certain populations.

“The goal has been to improve on that 50% protection,” Permar said.

Glycoprotein B is one of the viral surface proteins that helps CMV attach to human cells. It’s also one of five proteins that come together to form a structure called the pentameric complex, which CMV uses to enter and infect epithelial cells that line the nose and mouth. The new vaccine candidate targets both glycoprotein B and the pentameric complex.

The new study compared the immune responses elicited by both vaccines, particularly in terms of functional responses against the virus. Compared to gB/MF59, the new vaccine demonstrated better effectiveness in preventing CMV infection in epithelial cells. Additionally, the mRNA vaccine triggered the immune system to destroy CMV-infected cells more effectively.

“The older vaccine was slightly better at eliciting antibodies that can engulf the virus, what we call antibody dependent cellular phagocytosis,” Permar said. “Overall, though, these functional antibody responses that were not elicited by the glycoprotein B vaccine, which gives hope that the efficacy can be higher with this newer vaccine.”

A global phase 3 clinical trial (NCT05085366) of the mRNA-1647 vaccine is underway. The trial, called CMVictory, aims to determine if the differences in immune responses will result in better protection against CMV. The trial is testing the safety and efficacy mRNA-1647 vaccine for primary CMV infection in 8,000 women of child-bearing age.

“This is such an important vaccine pursuit, and it's exciting to see it go into phase three trials,” Permar said. She pointed out that this is the first phase three trial for any vaccine against CMV.

Permar also conveyed optimism regarding new and improved testing for CMV, which is an under-recognized infection.

“Previously, there were no universal testing programs for congenital CMV. However, two states in the US, Minnesota and New York, have begun universal testing, and others are expected to follow,” she explained. “With the development of preventative strategies and improved testing, we will be able to address CMV more effectively.”