UCLA scientists find secretory protein that may defeat tuberculosis
New discovery could yield treatment for high-mortality infection
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
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