By Marcelle Richards
Daily Bruin Contributor
UCLA researchers announced Tuesday that a tuberculosis vaccine
10 times stronger than the current vaccine may eventually be the
answer to a reduction in TB cases worldwide.
The current vaccine, bacillus Calmette-Guérin, was
developed nearly a century ago and until now, its effectiveness has
not been surpassed. Despite the prevalence of BCG’s usage,
though, TB accounts for the highest rates of mortality in the world
of any single infectious agent.
“In the world today, almost everyone in the developed
countries are vaccinated, yet despite this, there are still 8
million new cases and 2 million deaths every year,” said Dr.
Marcus Horwitz, principal investigator and UCLA professor of
medicine and microbiology, immunology and molecular genetics.
Gunter Harth, Barbara Jane Dillon and Sasa Maslesa-Galic, all
from UCLA’s School of Medicine, worked under Horwitz in the
study. Horwitz and his research team published their work in the
Nov. 28 edition of the Proceedings of the National Academy of
Sciences as the product of six years of research.
Though TB cases dwindled in the U.S. after scientists of the
1940s developed treatments for the disease, the frequency of
incidents began to rise again in 1984, according to the Centers for
Disease Control.
Inmates and those who are impoverished, foreign-born or
HIV-positive are more susceptible to TB.
“TB has traditionally been stigmatized the disease of the
poor because it spreads more easily where you have crowding or poor
sanitation,” said Meera Sreenizasan, Epidemiology Analyst for
the Los Angeles TB Control Program. “The medication’s
not there, the infrastructure’s not there.”
TB bacteria usually spreads through the air when an infected
person sneezes or coughs. Once the bacteria is inhaled, individuals
often have a 10 percent chance of developing an active form of the
disease, according to the National Institute of Allergy and
Infectious Diseases.
India, Russia, Eastern Europe and Southeast Asia show much
higher per capita infection rates for these reasons.
“It’s an indication of poverty, it’s a mark of
poor resources and an inability to treat current cases,”
Sreenizasan said.
While BCG is used to vaccinate 3 million people annually, its
variable efficacy ranges from 35 to 80 percent, which indicates
some may actually become infected after receiving the vaccine. The
average rate of successful prevention equates to one in two ““
a major weakness that prompted Horwitz and his associates to search
for a more potent vaccine.
Additionally, the BCG vaccine is often less effective in adults
who have been exposed to TB as children, according to
Sreenizasan.
“It’s questionable whether it has life-long
protection. Any vaccine proven more effective is most
welcome,” she said. “What it protects against is
developing the disease, not preventing infection.”
The National Institutes of Health decided to fund
Horwitz’s study because the quest for a more potent vaccine
remains a top priority for TB research. Upon seeing the potential
for a promising medical development, NIH sponsored Horwitz and his
crew.
Scientists have been searching for a new TB vaccine for the past
15 years, during which they tested 130 vaccines before a protein
produced in host cells proved most successful.
In the UCLA study, guinea pigs were injected with an extremely
virulent strain of TB. Horwitz battled the TB strain using
secretory proteins to test his theory that these proteins would
trigger a stronger immune system response.
Secretory proteins, which are released by infected host cells,
cling to the cell’s surface and attract fighter cells called
lymphocytes like bull’s eyes for the presence of disease.
Horwitz discovered this method led to an immune system response
ten times stronger than the response produced using BCG. The key
lies in inserting DNA that encodes secretory proteins into two
existing BCG stains. Since more secretory proteins are produced,
more lymphocytes are signaled to fight the TB strain.
“We had not anticipated that it would boost the response
as much as it did,” Horwitz said. “That was a pleasant
surprise.”
This recombinant vaccine adhered to Horwitz’s criteria for
a solution.
“It expressed the protein in its native form, just as
it’s expressed and secreted in the host. It had to be non –
pathogenic, and able to be produced in the host,” he
said.
With Horwitz’s team’s vaccine, the strong potency is
expected to drastically reduce the number of people infected, at a
relatively low cost.
“The vaccine is inexpensive to produce and administer,
which is a great advantage in developing worlds,” Horwitz
said. “If the vaccine works as well in humans, we hope there
will be a universal vaccine for children.”
The recombinant vaccine’s safety profile is almost
identical to that of BCG, Horwitz said. Thus, the similarities
reduce nearly all fears of unknown side effects and health
hazards.
Horwitz said he intends to further boost the potency, using the
same concept of increasing secretory proteins to increase an immune
system response.
The next step is testing the recombinant vaccine on human
subjects within the next year, said Horwitz, who hopes to see
widespread use of the new vaccine in the near future.
Original Graphic By VICTOR CHEN/Daily Bruin Web Adaptation By
Mike Ouyang/Daily Bruin