May 7, 2010 – Harvard/MIT researchers appear to have solved one of the great mysteries of HIV — and may at last be on track to develop an effective AIDS vaccine.
The mystery is why about one in 200 people infected with HIV — dubbed “elite controllers” — never get AIDS. It’s long been thought that solving this secret would lead to the Holy Grail of AIDS research: an effective vaccine.
Now researchers led by MIT’s Arup Chakraborty, PhD, and Harvard’s Bruce D. Walker, MD, report that elite controllers have a rare set of genes that allow their immune systems to unleash killer T cells with unusual powers. The findings come from an elegant series of experiments, including study of 1,100 elite controllers and 800 people with AIDS.
Normal killer T cells work as a team. It usually takes a swarm of these cells, which recognize different bits of a virus, to kill virus-infected cells. But this process is too slow to stop fast-mutating viruses such as HIV. The astonishing ability of HIV to change its spots via mutation is one reason the normal immune system can’t control the virus.
The killer T cells in elite controllers don’t need help. They knock off virus-infected cells all by themselves. Moreover, they are “broadly reactive” and can kill off mutant HIV variants as they arise.
There’s a downside to having broadly reactive killer T cells: They don’t always leave normal cells alone. This makes elite controllers more susceptible to autoimmune diseases.
But there’s an upside, too. Elite controllers aren’t just impervious to HIV. They’re also protected against other fast-growing viruses such as hepatitis C virus.
As it turns out, normal people have a few of these “broadly reactive” killer T cells. A few may be all that are needed.
“We think they might be coaxed into action with the right vaccine,” Chakraborty says in a news release.
Once activated and directed against HIV, these super killers would naturally expand by cloning themselves in large numbers.
The study drew praise from Nobel laureate and CalTech researcher David Baltimore, PhD.
“Rarely does one read a paper that stretches the mind so surprisingly far,” Baltimore says in a news release.
Chakraborty, Walker, and colleagues report their findings in the May 5 online issue of the journal Nature.