A vaccine developed at UC Davis to prevent cytomegalovirus (CMV) – an infection that can be severe among infants and life-threatening for the immunocompromised – delayed infection in monkeys by three months.
The UC Davis study, published today in Latest Articles in the Proceedings of the National Academy of Sciences, is the first to show that a vaccine can prevent transmission of CMV across mucosal surfaces, such as the mouth, nasal passages and airway.
“Developing a vaccine to control the spread of CMV has been a decades-long goal,” said Dennis J. Hartigan-O-Connor, senior author of the study and associate professor of medical microbiology and immunology at UC Davis.
“CMV is the most common congenital infection in the U.S. While most infants will have no permanent health problems, some will develop severe consequences, from hearing loss, developmental delay and vision problems. Preventing congenital infection is a public health priority,” he said.
Unique approaches to CMV vaccine
The UC Davis team used a unique study design and approach to develop the vaccine. They designed the study to simulate how the virus spreads among young children at daycare or in schools.
“Infants and toddlers are thought to be an important way that the virus spreads to women who may be pregnant, which endangers their developing fetuses,” Hartigan-O’Connor said. “While typical vaccination studies directly infect each animal, we housed healthy monkeys with CMV-infected cage-mates. In this environment, the monkeys were exposed to the virus continuously.”
The researchers also specifically targeted viral interleukin-10 (vIL-10), a protein the virus uses to prevent the immune system from responding to the infection. Other vaccines normally target proteins located on the outside surface of the virus that initiate the infection, said Jesse Deere, first author of the study and a scientist in the Department of Medical Microbiology and Immunology at UC Davis Health.
“Our vaccine targeted vIL-10, which the virus uses to suppress how an infected host responds to infection,” Deere said. “By disrupting this viral protein with the vaccine, we delayed infection and altered the long-term immune responses when monkeys got infected.
“We will continue testing the vaccine, making further adjustments and moving toward human clinical trials,” he said.
UC Davis is uniquely suited for this research. It has a large national primate research center, school of veterinary medicine, medical school and research laboratories. This infrastructure allows scientists to develop and evaluate novel vaccine strategies from initial concept to testing in nonhuman primates and in people.
Working to prevent CMV infection in pregnant women
Deere believes an effective vaccine to prevent CMV infection would improve global health.
“CMV spreads from an infected person by direct contact with saliva or urine, especially among babies and young children. Most pregnant women acquire infection as a result of contact with their own younger children, or children in daycare or school. A CMV vaccine in infants and toddlers would help to prevent infections in pregnant women, reducing the chance that their babies become infected and develop disabilities,” Deere said.
“Research is needed to understand the mechanisms of viral persistence, approaches to preventing fetal infection in pregnant women and development of anti-herpesvirus chemotherapies,” he said.
CMV is one of the herpes viruses and is related to the viruses that cause chickenpox, cold sores and mononucleosis. According to the U.S. Centers for Disease Control and Prevention, nearly one in three U.S. children are infected with CMV by age five, and more than half of adults are infected by age 40. While healthy people rarely experience problems, the virus remains in the body throughout the lifespan.
Infected persons of any age periodically shed the virus in their body fluids, such as saliva, urine, blood, tears, semen or breast milk. CMV can also be transmitted through organ and stem cell transplants. CMV in people with compromised immunity can affect the brain, spinal cord, lungs and intestines. It can also lead to organ rejection or graft-versus-host disease in transplant patients.
Other authors of the study “Neutralization of rhesus cytomegalovirus IL-10 reduces horizontal transmission and alters long-term immunity” include: W.L. William Chang, Andradi Willalobos, Kim A. Schmidt, Luis D. Castillo, Joseph Fike, Ashlesha Deshpanade and Mark R. Walter. Hartigan-O-Connor works at UC Davis and the University of Alabama, Birmingham.
The research was funded with grants from the National Institutes of Health (A1097629, A1049342, A1143554, A1131568 and P51OD011107).