An experimental vaccine modeling human cytomegalovirus (HCMV) infection — which can endanger developing fetuses, transplant recipients, patients co-infected with HIV and others who have a weakened immune system — proved safe and effective in research conducted at the CNPRC using the rhesus macaque model.
A team of scientists from the CNPRC, UC Davis Center for Comparative Medicine, and the University of Alabama, Birmingham, led by Peter Barry, PhD, CNPRC Infectious Diseases Core Scientist, developed the first-of-its-kind approach to preventing HCMV infection inducing broader immunological protection in rhesus monkeys. The publication describing the research is entitled: “Vaccination Against a Virally-Encoded Cytokine Significantly Restricts Viral Challenge”, November 2013, Journal of Virology.
Development of an HCMV vaccine has been ranked as the highest priority by the Institute of Medicine, an independent agency of the National Academy of Science, because of “the lives it would save and the disabilities it would prevent,” according to the U.S. Centers for Disease Control and Prevention.
“We’ve completed the first step in developing a vaccine to protect people against HCMV by interfering with the virus’s attempts to enter and infect cells in the body,” said Dr. Barry.
HCMV 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 HCMV infections are not diagnosed because the virus typically causes few, if any, symptoms. As a result, most people infected are unaware that they harbor the virus — a condition that is of most concern among pregnant women, who are at risk for acquiring the virus from a close contact and subsequently transmitting the virus to her fetus.
Children who are congenitally infected may have cognitive and other developmental disabilities, including hearing loss and blindness. HCMV is the most common viral cause of congenital defects in the United States. About one in 150 children in the U.S. is born with congenital HCMV. About one of every five children with congenital HCMV infection — a total of 5,000 children each year — will develop hearing loss or developmental disabilities due to the infection, according to the Centers for Disease Control.
Because previous vaccine approaches failed to provide complete protection against HCMV infection, Dr. Barry and his collaborators adopted an “out-of-the-box” approach when designing the new vaccine. They focused on the virus’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 vaccines.
“HCMV is not like the influenza virus, which our immune systems can successfully clear from our bodies. HCMV infection is persistent,” Dr. Barry said. “Once you’re infected, you’re always infected.”
The virus’ persistence and ability to infect individuals without creating obvious symptoms of infection help explain why HCMV can be found in 50 to 80 percent of people under the age of 40.
The key to HCMV’s persistence, Dr. Barry and his 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.
Through his extensive research at the CNPRC, Dr. Barry previously discovered that early in its evolutionary history HCMV hijacked IL-10 and incorporated this gene into the virus’s own DNA code. As a result, HCMV can manipulate the body’s normal immune response to the virus.
In developing their vaccine strategy, the researchers focused on neutralizing HCMV’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 monkeys did not become infected because, as a result of the vaccine, their immune systems generated neutralizing antibodies that prevented HCMV from entering and infecting connective tissue cells, epithelial cells and other major cell types that the virus targets,” Dr. Barry said.
“The vaccine also created ‘immunological memory,’ which enables the immune system to respond quickly and effectively whenever HCMV re-infection occurs.”
Dr. Barry has been focusing his research on HCMV using the rhesus macaque model his lab began developing over 25 years ago. The work with the rhesus model, including the vaccine based on viral IL-10, could only have been possible here at UC Davis and the CNPRC. “This research is an example of the critical importance of the monkey model, the preeminent position of UC Davis in research that has important clinical outcomes, and the demonstration of taxpayers’ money being used to improve the human condition” emphasizes Dr. Barry. Long-term goals include advancing the results from the monkey studies into human clinical trials.