University of Nebraska Medical Center scientists have developed a prototype
model for a vaccine against myocarditis, an often deadly form of heart
disease, by genetically altering one of the very viruses that cause the
disease.
Myocarditis is an acute inflammation of the heart muscle that can be
caused by specific viruses. The most common viruses that cause myocarditis
are the group B coxsackieviruses and human adenoviruses.
Principal investigators Steven Tracy, Ph.D., professor, and Nora Chapman,
Ph.D., associate professor, both of the Department of Pathology and Microbiology,
used a group B coxsackievirus (CVB) and the human adenovirus type 2 to
develop a new vaccine delivery system in a mouse model.
CVB causes acute myocarditis, an inflammatory disease of the heart muscle,
and dilated cardiomyopathy, in which the heart muscle becomes quite large.
Every year worldwide, five to eight people per 100,000 suffer from dilated
cardiomyopathy and about two people per 100,000 have myocarditis.
The uncertainty of the number of cases of myocarditis stems from an
inability to readily detect the disease. Dilated cardiomyopathy, however,
is often associated with signs of a failing heart. Of these cases, about
25 percent, or about 13,000 people in the U.S., are thought to be associated
with CVB each year. Unfortunately, most of these cases remain undiagnosed.
There are six different types, known as serotypes or species, of coxsackie
B viruses and probably at least two types of adenoviruses that cause heart
disease in humans, Dr. Tracy said.
Coxsackieviruses are enteroviruses, common human viruses that usually
do little harm. Infections with coxsackieviruses are common and most young
adults have had at least one or two such infections.
Adenovirus is another common human virus that is generally associated
with upper respiratory symptoms in humans.
Natural infection is the only way by which a person becomes immune,
as there are no commercially-available vaccines available against these
viruses.
The researchers, who have been studying these viruses for 18 years,
published the results of their study in the May issue of the Journal of
Virology.
CVB induces a vigorous immune response in the person who is infected.
As both CVB and adenoviruses cause heart disease, it made sense to use
one of the viruses as a vehicle to immunize against the other, said Dr.
Chapman.
Mice that were inoculated with this vaccine made protective antibodies
against both CVB3 and adenovirus. Interestingly, the virus worked as a
vaccine even in mice that had been previously vaccinated against the specific
coxsackievirus.
This is a key finding, Dr. Tracy said. Because coxsackieviruses are
common virus infections in humans, many people already have antibodies
against some of them. It was possible that in such people, CVB-based vaccines
would have little effect. However, we found that vaccination of mice that
were already immune to the virus actually had a better immune response
to the model hybrid vaccine. This finding suggests that a single virus
has the potential to be used effectively as a vaccine delivery system many
times in one patient.
Drs. Tracy and Chapman are now working to create a similar hybrid virus
that induces protective immunity against all six group B coxsackievirues
as well as against specific adenoviruses.
Also in the May issue of the Journal of Virology, Drs. Tracy and Chapman
published results describing how they have altered enteroviruses to provide
a new approach to generating modified vaccine strains of virus. In addition,
they also published results of a collaborative study with another UNMC
researcher, Jose Romero, M.D., associate professor in Pediatrics/Infectious
Disease. This study showed, for the first time, the location of the genetic
instructions for coxsackievirus RNA that can cause heart disease.
Drs. Tracy and Chapman recently received a $300,000, two-year grant
from the National Institutes of Health to explore this same hybrid vaccine
technology against the human immunodeficiency virus (HIV), the virus that
causes AIDS.
Dr. Tracy and his collaborators are members of the UNMC Enterovirus
Research Laboratory that studies enterovirus heart disease. The UNMC Enterovirus
Research Laboratory maintains an informational Web site called Coxsackieviruses
and Viral Myocarditis [http://www.unmc.edu/Pathology/Myocarditis].