|Experimental Vaccine Shows Promise in Preventing Cytomegalovirus Infection
Each year, approximately 8,000 infants in the United States develop severe hearing,
mental or movement impairments after becoming infected with cytomegalovirus
(CMV), a common virus passed onto them while still in the womb.
Now, published results of a trial involving 441 CMV-negative women
give rise to optimism that a vaccine to prevent congenital CMV
may be closer. Women who received the trial vaccine were 50 percent
less likely to later become infected with CMV than were women who
received a saline injection.
The National Institute of Allergy and Infectious Diseases (NIAID), part of the
National Institutes of Health (NIH), sponsored the trial. The research
team, led by pediatrician Robert Pass, M.D., of the University
of Alabama at Birmingham, published their findings in the current
issue of the New England Journal of Medicine.
"This trial demonstrates that a statistically significant degree of protection
against maternal CMV can be achieved through vaccination," says Dr. Pass. "This
is an important step along the path towards the ultimate goal — a vaccine that
can protect infants from congenital CMV infection." He notes that a larger trial
would be needed to conclusively prove the efficacy of any candidate CMV vaccine
for this purpose. "However, for everyone interested in CMV vaccine development,
this is an encouraging result."
The trial evaluated an experimental vaccine made from a single CMV protein, glycoprotein
B, which is known to provoke an immune response. The candidate vaccine, supplied
by sanofi pasteur (Lyon, France), included an experimental adjuvant, MF59. An
adjuvant is a substance added to a vaccine to improve the immune system response
The clinical team invited healthy women between the ages of 14 and 40 who had
given birth at the University of Alabama at Birmingham or at the University of
Alabama College of Community Health Sciences in Tuscaloosa to participate in
the trial. Of the 18,463 women they screened, approximately 24 percent were CMV-negative.
This rate is consistent with figures from the Centers for Disease Control and
Prevention, which estimates that between 50 and 80 percent of adults are infected
with CMV by age 40.
After nearly seven years, the trial reached its enrollment goal. A total of 441
CMV-negative women, divided at random to receive the candidate vaccine or a saline
injection, were evaluated. Vaccinations were given to women within one year after
they had given birth. Most women received three doses of trial vaccine or saline
injection; all received at least one dose. All the volunteers agreed to use birth
control until two months after receiving the final injection.
In the final analysis, women who received the trial vaccine were significantly
more likely to remain uninfected throughout the 42-month follow-up period than
those who received the saline injection. Eight percent of vaccine recipients
(18 of 225) eventually became infected with CMV, while 14 percent of saline injection
recipients (31 out of 216) acquired a CMV infection by the end of the trial.
There were no significant differences between the trial vaccine group and the
saline injection group in frequency of fever, nausea, fatigue or rash. Most of
the body-wide reactions were mild and lasted less than a day. Local reactions — such
as pain, redness and swelling at the injection site — occurred more often in the
vaccine group than in the group receiving saline injection. The majority of local
reactions lasted less than a day.
Aspects of CMV biology have caused skeptics to question whether it is possible
to prevent infection through vaccination, explains Dr. Pass. The virus is well
adapted to persist in an infected person and is readily passed from person to
person through direct contact with numerous bodily fluids: urine, saliva, breast
milk, tears, blood, semen and vaginal fluid. Healthy people typically experience
no symptoms after being infected with CMV. There is a strong immune response
to the initial infection, but this immunity cannot always prevent subsequent
infections if a person re-encounters the virus. Finally, natural infection does
not elicit a response sufficient to completely eliminate the virus. On the contrary,
once a person is infected, the virus persists for life.
Two additional NIAID-supported Phase II trials of the experimental CMV vaccine
are under way. One trial is enrolling adolescent girls; the other trial has enrolled
volunteers who are awaiting liver or kidney transplants. The immunosuppressive
drugs taken by transplant recipients can make them vulnerable to illness if they
become infected with CMV following the organ transplant. The NIAID-sponsored
trial will test whether the candidate CMV vaccine can boost the immune system
enough to prevent illness from CMV. Further information about these trials (NCT00133497
and NCT00299260) can be found at www.clinicaltrials.gov.
Through its General Clinical Research Centers program, the NIH’s National Center
for Research Resources provided laboratory and nursing assistance support for
the CMV vaccine trial in women.
NIAID conducts and supports research — at NIH, throughout the United
States, and worldwide — to study the causes of infectious and immune-mediated
diseases, and to develop better means of preventing, diagnosing and treating
these illnesses. News releases, fact sheets and other NIAID-related materials
are available on the NIAID Web site at http://www.niaid.nih.gov.
The National Center for Research Resources, a part of NIH, provides
laboratory scientists and clinical researchers with the resources and training
they need to understand, detect, treat and prevent a wide range of diseases.
NCRR supports all aspects of translational and clinical research, connecting
researchers, patients and communities across the nation. For more information,
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.
Reference: RF Pass et al. Vaccine prevention of maternal cytomegalovirus infection. New
England Journal of Medicine. 360: 1191-9 (2009) Further information about this trial (NTC00125502) can be found at www.clinicaltrials.gov.