Future Shot
The arsenal of vaccines continues to grow as researchers create
new tools to halt deadly diseases and infections.
In 1796, smallpox was howling through Europe,
leaving in its wake countless dead, disfigured and blind. For some
reason, milkmaids as a group seemed to be immune to the disease.
Observing this in pastoral Gloucestershire, England, physician Edward
Jenner noted that dairy workers who avoided smallpox seemed to have
one thing in common; virtually all of them had suffered previous
bouts with cowpox, a relatively mild malady The former British army
surgeon theorized that the cowpox infection itself had protected
the milkmaids from the smallpox virus.
Jenner enlisted the aid of a local gardener's eight-year-old son
in what might be the first clinical trial in immunology. The doctor
took cowpox material from a milkmaid, applied it to a metal strip
and scratched it into the youngster's arm. As expected, the boy
developed cowpox. When the lad recovered, Jenner scratched smallpox
matter into his arm - and waited. Then, just as the country doctor
had theorized, something amazing happened.
Absolutely nothing.
Jenner called his discovery "vaccine" and the method
of delivering it a "vaccination." While it would be 1980
before the World Health Organization would pronounce smallpox dead
on a global scale, Jenner's work set the stage for research and
technology that ultimately conquered or controlled other contagious
diseases. Today, many diseases have been nearly eliminated in the
industrial nations, and WHO predicts that both measles and polio
will be eradicated worldwide within the next two years.
As our understanding of viruses and the human immune system grows,
so does scientists' ability to create a new class of vaccines to
prevent, treat or possibly cure AIDS, sexually transmitted disease,
malaria, Alzheimer and Lyme diseases and some forms of cancer.
Until recently, vaccines typically have been made from naturally
occurring bacteria or viruses (living and dead) or from their byproducts.
The pox vaccine that Dr. Jenner discovered and the polio vaccine
Jonas Salk developed in 1955 both used "dead" viruses
to immunize patients, which eliminated the risk of infecting them.
Today's genetically engineered vaccines are different in structure;
most of those under investigation exclude the DNA of the virus and
are unable to produce an infection. At the Indiana University School
of Medicine, genetically engineered vaccines are in development
for STDs and for some forms of cancer.
Kenneth H. Fife, MD, PhD, professor of medicine, and Darron Brown,
MD, associate professor of medicine and of microbiology and immunology,
and their colleagues in the Division of Infectious Diseases are
investigating a preventive vaccine for the sexually transmitted
human papillomavirus type 11 (HPV 11), a common cause of genital
warts. Some of the thirty-five types of genital HPV affecting between
twenty-four to forty million Americans, are known to cause cancer,
though HPV 11 is not among them. Currently, there are no vaccines
for any strain of HPV
The DNA from HPV 11 has been treated so that only the gene for
the major coat protein of the virus remains. This isolated gene
is then placed in a yeast cell under conditions that cause the yeast
to make large quantities of the protein. The protein automatically
assembles into a product called a virus-like particle (VLP), consisting
of the shell of the virus without any other proteins or any genetic
material. This VLP is not able to cause infection. Like other vaccines,
the VLP is injected intramuscularly to activate the body's immune
system - in this case, with HPV 11-fighting antibodies - against
a future exposure to the virus.
In the trial for the HPV 11 vaccine, 140 healthy women between
eighteen and twenty-five were divided into groups to receive differing
dosages of the vaccine, then monitored closely. "Overall, the
injections were well tolerated by the participants," notes
Dr. Fife, who presented his findings at a symposium last July in
Barcelona, Spain. "About half had soreness near the injection
site; others had redness, both common reactions for any kind of
vaccination."
"Nearly all of the women who received VLPs developed neutralizing
HPV 11 antibodies by the seventh month," adds Dr. Brown, who
also presented at the Barcelona gathering. As this issue went to
press, the final results of the clinical trial, which was funded
by Merck and Company, were not available. Still, Dr. Fife says that
the initial findings are promising enough to warrant a further study
of the HPV 11 vaccine's effectiveness.
HPV is not the only sexually transmitted disease IUSM scientists
have targeted for genetically engineered vaccines. In recent years,
Dr. Fife also investigated gene vaccines for genital herpes, one
targeting atrisk couples (one partner with the disease) and two
others for individuals at varying risk of infection. One vaccine
was virtually ineffective, Dr. Fife says, adding that both vaccinated
and unvaccinated (placebo) subjects tended to contract the herpes
virus at the same rate. The second vaccine showed promise in some
patients and will require further study to determine which patients
may benefit from its use.
Dr. Fife continues to research possible vaccines for herpes. Dr.
Brown is opening new clinical trials for other papillomavirus vaccines
directed at other types of HPV
Boosting The Immune System To Fight Cancer
IUSM researchers also are taking aim at cancer with genetically
engineered vaccines. One early clinical trial is testing two vaccines
for prostate cancer that has spread beyond the gland.
In this Phase 11 clinical trial, Christopher Sweeney, MD, an oncology
fellow at the IU Cancer Center, seeks to stimulate the immune system
to destroy malignant cells before they become symptomatic, while
sparing healthy tissue.
"We want to see if the vaccines will boost the patient's immune
system and eliminate the cancer while it is still at a relatively
low level in the body" Dr. Sweeney says. "We're testing
two vaccines to determine which treatment regimen is most effective.
One uses the vaccinia virus, a relatively harmless virus used to
vaccinate against smallpox, the second uses the fowlpox vaccine."
Participants are divided into three groups, each receiving injections
over a six-month period. Two groups receive a series of 12 injections
of predominantly eithcr the \ accinia virus or the fowlpox strain;
the third group receives only the fowlpox vaccine.
Both viruses are genetically altered in the laboratory to express
human prostate specific antigen (PSA). Since patients enrolled in
this trial already have undergone radiation therapy or removal of
the prostate, their PSA levels should be at very low or undetectable
levels. The only evidence of recurrence would be the elevated PSA.
IUSM researchers are collaborating in the trial with the seven
other U.S. medical research centers that are part of the Eastern
Cooperative Oncology Group (ECOG), one of several regional networks
overseen by the National Cancer Institute to coordinate clinical
cancer research.
As IUSM scientists continue their work with genetically altered
viruses, they feel certain that medicine will eventually devise
new vaccines which can safely manipulate the immune system. The
School's strong base in immunology and biochemistry qualifies its
participation in these novel approaches to disease control.
|
