
OCTOBER 24: A new kind of test and a new understanding of the human immune system may help researchers figure out how to vaccinate against the centuries-old scourge of tuberculosis.
Scientists said on Monday they had found three proteins that the human body uses to recognise and fight TB, and they are now designing a vaccine to test based on the proteins.
The researchers, at San Diego-based Epimune Inc., the University of California, Los Angeles, Harvard University and elsewhere, said the vaccine approach involves a new component of the immune system not usually used in vaccinating against disease.
“In general, a lot of the vaccines that are out there are very good at inducing anti-bodies,” Alessandro Sette, an immunologist at Epimune who worked on the study, said in a telephone interview.
Anti-bodies are produced by the immune system to flag invaders, such as bacteria, so other cells can clear them out. Anti-body vaccines work well against viruses such as polio and smallpox.
But other bugs are trickier, and efforts to design a vaccine against Hepatitis-C, HIV and TB have not worked so well.
Recently, AIDS researchers have found that another component of the immune system, the killer T-cells, also known as CD8 cells or cytotoxic T-lympocytes, might be a better force to use against these tough-to-fight microbes.
The same might be true for TB, which kills three million people a year and which has resurfaced in a drug-resistant form.
Writing in the proceedings of the National Academy of Sciences, Sette and colleagues said they used Epimmune’s screening system to find proteins from the tuberculosis bacillus that would excite a CD8 response.
They chose 40 proteins and first ran them through a computer programme to identify the ones they thought were the most likely candidates.
They tested the best ones in the laboratory to see if they produced an immune system response. Three did, Sette said.
“They fit the bill of what is understood today as a meaningful response against the pathogen,” he said. The three were recognised by CD8 cells taken from patients who had recovered from TB infection.
When exposed to the proteins, the CD8 cells went into killing mode, producing a compound called interferon gamma that bursts apart an infected cell to kill the invader.
Now Epimune is trying to develop a vaccine based on the proteins and organise testing of it, Sette said.
In searching for the proteins, the scientists used an approach also used by AIDS researchers — finding people who have a natural immunity and finding just what it is about them that makes them fight the infection so well.
“What you are trying to look for are people that are recovering from infection, or the famous long-term non-progressors in HIV, or if they have hepatitis, people that have had acute hepatitis and recovered,” Sette said.


