Experimental vector vaccine reduces stillbirths from cytomegalovirus

Feb 21 2007

Researchers funded by the National Institutes of Health have developed an experimental vaccine that reduces stillbirths among rodents born to mothers infected with cytomegalovirus (CMV) - a common virus that can also cause mental retardation and hearing loss in newborn children who were infected in early fetal life.

Estimates place the number of U.S. children born with CMV each year at about 40,000, and there is no vaccine or treatment for pregnant women who have the infection. In a 2000 report, the Institute of Medicine of the National Academy of Sciences listed as a top priority the development of a vaccine to prevent cytomegalovirus during pregnancy.

"An effective CMV vaccine for women of childbearing age could greatly reduce the disability caused by the virus," said Duane Alexander, M.D., Director of the NICHD, the NIH institute that funded the study. "A prototype vaccine is the first step in protecting newborns against the most common viral disease of newborns in the developed world."

The study appears in the March 15, 2007, issue of the Journal of Infectious Diseases.

Mark Schleiss, M.D., American Legion Endowed Chair in Pediatric Infectious Diseases at the University of Minnesota School of Medicine, led a team of researchers at his own and other institutions to conduct the study.

Female guinea pigs given the CMV vaccine before becoming pregnant gave birth to fewer dead pups and were less likely to transmit the infection to their offspring than were female guinea pigs not receiving the vaccine.

The vaccinated group (10 litters) produced 28 live pups and 4 dead pups - a mortality rate of 13 percent. The control group (8 litters), which received a vaccine for the flu, produced 9 live pups and 12 dead pups - a mortality rate of 57 percent.

The surviving pups weighed more than the pups of mothers that had not received the CMV vaccination before becoming pregnant. The vaccine greatly reduced the total amount of virus found in the mothers' blood. The vaccine in the study was developed in collaboration with researchers at AlphaVax, Inc.

CMV is a common viral infection related to the herpes virus and often causes few or no symptoms, according to the National Institute on Deafness and Other Communication Disorders. Every year, 0.5 to 2.5 percent of babies born in the United States are infected with CMV. The virus is transmitted to the fetus through the mother's placenta.

Dr. Schleiss said that 10 percent to 15 percent of babies with congenital CMV have a long-term disability such as mental retardation, cerebral palsy, and hearing loss. The infection could potentially cause other developmental disabilities such as autism or attention deficit disorder. The virus can also damage the placenta, leading to pregnancy loss.

CMV is present in bodily secretions and is spread through close personal contact, such as kissing or sharing eating utensils. For example, an infant in daycare could give the virus to her pregnant mother by kissing her on the lips, said Dr. Schleiss. The virus can enter through mucosal surfaces such as the mouth or breaks in the skin. It can also be transmitted through nasal secretions, blood transfusions, and sexual contact. Most adults will become infected with CMV at some point during their lives. Dr. Schleiss added that pregnant women may not even know they have the infection.

The experimental vaccine differs from traditional vaccines, which are made from a whole killed virus. Called a vector vaccine, the experimental vaccine uses an altered virus to deliver one gene from the viral DNA to the animal's cells. The cells then begin manufacturing the viral protein. Cells of the guinea pigs' immune system detect the viral protein and launch an attack against it. In so doing, they learn to recognize CMV. The gene used in the experimental guinea pig CMV vaccine - UL83, also called pp65 - contains the information needed to make a protein involved in the infection process. The virus used to make the vector vaccine (Venezuelan Equine Encephalitis Virus) was altered by removing 40 percent of the virus' genes, to prevent it from reproducing and infecting new hosts.

The young female guinea pigs in the study were vaccinated three times at two-month intervals before they became pregnant and were injected with the guinea pig form of CMV early in their third trimester.

Tests showed that the rodents given the experimental vaccine had acquired immunity to guinea pig CMV because they produced antibodies to the virus - proteins that target foreign molecules for later destruction by the immune system. The vaccinated guinea pigs also showed an activity against the virus by their T cells, immune cells critical to the response against disease-causing organisms.

Dr. Schleiss said the current paper provides the basis for the potential development of a version of the vector vaccine that could be tested in human beings.

The NICHD sponsors research on development, before and after birth; maternal, child, and family health; reproductive biology and population issues; and medical rehabilitation.

http://www.nichd.nih.gov/