Scientist Peter Nara uses a blue water bottle as a model of a "good" antibody, with "poor" and "ugly" antibodies in different colours. (Armina Ligaya/CBC)
A vaccine for HIV remains a holy grail in fighting the epidemic. The winding path to finding a vaccine reveals the tenacious nature of the virus, as well as the small discoveries along the route to a potential breakthrough.
Over 200 years, the research and development of vaccines has progressed from simply injecting cowpox vaccine to stimulate immunity against smallpox to attempts to protect people from more scientifically challenging foes such as influenza and HIV.
While the first vaccines used a dead or weakened virus to prime the immune system, today's vaccines often use just key proteins from the pathogen.
Early or Class I vaccines protect children who haven't had years to build up natural immunity from exposure to circulating viruses.
If all of the infectious bacteria and viruses are pictured as an iceberg, the Class I vaccines are just the tip.
The more difficult and sophisticated Class II vaccines scientists are trying to develop to combat AIDS lie under the waterline, said Peter Nara, a veterinary researcher who left the U.S. National Cancer Institute to work on an AIDS vaccine at Biological Mimetics Inc. of Fredrick, Md.
The HIV is a wily target for scientists because it:
- Integrates itself quickly into the DNA of cells.
- Mutates frequently, not only between hosts but also within a person.
For a vaccine to work, it needs to have high immunogenicity — the immune system needs to be able to see the foreign invader's protein shape and mount an effective response to it.
It's like a bull challenging a matador, with the immune system as a bull. The matador's cape acts a decoy, misdirecting the bull from the man.
In the case of HIV, the body's antibody response is too slow and too narrow, so the virus escapes while the immune system is distracted by a decoy, Nara explained in a presentation to the 16th International AIDS Conference in Toronto.
The technology Nara is working on removes the decoy so the immune system can attack the most vulnerable parts of the virus, a step that's needed for an HIV vaccine to work.
It's a strategy that has worked for commercial vaccines for similar class II viruses that hurt the swine and aquaculture industries, as well as goats, Nara reported. It could apply to other diseases such as HIV, influenza, common cold viruses and hepatitis.
"The pipe dream is looking a little less like a dream," Nara said.
One problem is that antibodies come in good, bad and ugly forms. In the bad case, the immune response is too narrow, allowing the virus to escape. In the ugly case, antibodies are co-opted into actually helping the virus, instead of fighting it.
When the body reacts to HIV, it makes few good and many bad and ugly antibodies, while the immune response overall is too slow, Nara told CBC News Online.
AIDS facts and figures
A group of Kenyan prostitutes seem to have some type of immunity to HIV. A study of them by a Canadian researcher is helping to reveal differences between antibodies.
In 1990, researchers at the University of Manitoba gained some clues about the differences between antibodies by studying a group of prostitutes in Kenya who weren't infected, even though they regularly had unprotected sex.
Experts believe that something genetic is protecting the Kenya women. A small proportion of men who have sex with men in the developed world have also shown a similar type of protection.
"We're more and more convinced that they have some kind of immunity to HIV," said Dr. Frank Plummer, who leads the research on prostitutes in Kenya at the National Microbiology Laboratory in Winnipeg.
"We can show that they have white blood cells circulating in their blood and also in the genital tract that will recognize and kill HIV-infected cells."
Plummer hopes to develop a vaccine that will provide the same immunity to HIV that the sex workers have naturally.
Adding to the puzzle though, he's also found the prostitutes' immunity often lapses when they leave the sex trade. If they're exposed to HIV again then they can become infected — a finding that points to an acquired immunity that needs continual boosting, he said.
Researchers are now intensely trying to find and test potential vaccines. Dozens have been developed and tested in animal models but only one has been tested in large-scale trial in humans, and it didn't work.
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Scientist Peter Nara uses a blue water bottle as a model of a "good" antibody, with "poor" and "ugly" antibodies in different colours. (Armina Ligaya/CBC)