Early tests of an experimental vaccine to prevent cytomegalovirus (CMV) infections in people suggest that it is safe and effective.
CMV is a type of herpes virus that is spread through close contact with the saliva, urine, or other body fluids of a person infected with the virus. Most CMV infections are not diagnosed because the virus typically causes few, if any, symptoms.
As a result, most people infected with CMV are unaware that they harbor the virus—a condition that is of most concern among pregnant women, who are at risk for transmitting the virus to the fetus. The virus also poses a threat to organ transplant recipients, patients with HIV, and others who have a weakened immune system.
The Institute of Medicine, an independent agency of the National Academy of Science, has set developing a CMV vaccine as the highest priority because of “the lives it would save and the disabilities it would prevent,” according to the US Centers for Disease Control and Prevention (CDC).
Symptoms in children
Children who are congenitally infected with CMV may have cognitive and other developmental disabilities, including hearing loss and blindness.
CMV is the most common viral cause of congenital defects in the US. While most of these children will not develop symptoms or problems, about 1 of every 5 children with congenital CMV infection—a total of 5,000 children each year—will develop hearing loss or developmental disabilities due to the infection, according to the CDC.
“We’ve completed the first step in developing a vaccine to protect people against CMV by interfering with the virus’s attempts to enter and infect cells in the body,” says Peter A. Barry, a professor of pathology and laboratory medicine at the UC Davis School of Medicine and lead author of the study published in the Journal of Virology.
Because so many previous vaccine approaches failed to provide complete protection against CMV infection, Barry and his collaborators adopted an “out-of-the-box” approach when designing the new vaccine.
They focused on CMV’s ability to gain a lifelong foothold in the body, a stage of the virus’s life cycle that no other research lab has targeted in research on potential CMV vaccines.
“CMV is not like the influenza virus, which our immune systems can successfully clear from our bodies. CMV infection is persistent,” Barry says. “Once you’re infected, you’re always infected.”
The virus’s persistence and ability to infect individuals without creating obvious symptoms of infection help explain why CMV can be found in 50 to 80 percent of people under the age of 40.
CMV also can infect animals, including rodents and rhesus macaque monkeys and other non-human primates. However, the CMV species found in animals differs from human CMV and has not been reported to cause human disease.
Immune system response
The key to CMV’s persistence, Barry and colleagues theorized, is interleukin-10 (IL-10), the master regulator of the immune system, which works to rein in an over-zealous immune response to an invading pathogen.
Barry previously discovered that early in its evolutionary history CMV hijacked IL-10 and incorporated its genes into the virus’s own DNA code. As a result, CMV can manipulate the body’s normal immune response to the virus.
In developing their novel vaccine strategy, the researchers focused on neutralizing CMV’s own IL-10 so that the immune defense system was again capable of responding vigorously and effectively to the presence of the virus.
“We found that the animals did not become infected because, as a result of the vaccine, their immune systems generated neutralizing antibodies that prevented CMV from entering and infecting connective tissue cells, epithelial cells, and other major cell types that the virus targets,” says Barry.
“The vaccine also created ‘immunological memory,’ which enables the immune system to respond quickly and effectively whenever CMV re-infection occurs,” he adds.
Based on these positive results, the researchers will evaluate the vaccine’s effectiveness and safety in an experimental setting that allows CMV-infected and vaccinated animals to interact, transmitting the virus as it typically would in the wild.
By comparing rates of CMV infection in the vaccinated and non-vaccinated animals, the research team will determine whether the vaccine alters the natural course of CMV infection and should be considered for clinical studies with humans.
The National Institutes of Health, the Margaret Deterding Infectious Disease Research Support Fund, and the California National Primate Research Center supported the work. Additional researchers from UC Davis and the University of Alabama, Birmingham, collaborated on the project.
Source: UC Davis