|Experimental Vaccine Given During Pregnancy
Reduces Stillbirths from Common Virus
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
“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
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.
Information about CMV infections acquired before birth is available
from NIH’s National Library of Medicine at http://www.nlm.nih.gov/medlineplus/ency/article/001343.htm.
CMV Vaccine Prototype
More information about CMV is available from NIH’s National Institute
of Allergy and Infectious Diseases at http://www.ninds.nih.gov/disorders/cytomegalic/cytomegalic.htm.
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. For more information, visit
the Institute’s Web site at http://www.nichd.nih.gov/.
The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and
Centers and is a component of the U.S. Department of Health and
Human Services. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and
its programs, visit www.nih.gov.