There are two traditional methods for creating a vaccine. One uses a weakened or attenuated version of a live virus to generate an immune response. The other uses a dead virus. Both methods are proven safe and effective, except when it comes to HIV. Vaccine candidates using these methods simply have not been successful in people when it comes to the AIDS virus.
“HIV has been a very difficult target for a vaccine for a variety of reasons. It’s designed to evade the immune response by evolution,” said Dr. Louis Picker, associate director of Oregon Health and Science University.
While attempts to make an HIV vaccine from a dead virus have failed, Picker said, using a weakened virus holds clues and possibilities when used in primates.
“The live attenuated approach actually was shown to work 20 years ago. But the problem with it was the live attenuated vaccines that actually worked were actually still pathogenic. So they weren’t safe and they could not be moved into humans. This was demonstrated in the non-human primate models – monkey model of AIDS using the virus SIV,” he said.
SIV stands for simian immunodeficiency virus.
“These SIVs that were attenuated, that prevented subsequent infection with the full pathogenic virus, still could cause disease. And people found that if you attenuated them anymore, they didn’t work anymore,” he said.
Picker and his colleagues wanted to understand why the weakened virus offered protection from infection. But at the same time, they needed to prevent it from itself causing disease. They found the answer has to do with T cells, which attack viruses. The weakened, but persistent virus vaccines somehow caused T cells to be ever vigilant. But if the virus was weakened too much, the T cells were not triggered to attack. They concluded that an “effective HIV vaccine might have to persist in the body.”
Picker said, “The unique aspect of the live attenuated vaccines that seem to work was that they were persistent. They weren’t cleared by the host immune system, but they were able to stick around. Of course in the case of HIV/SIV that’s a bad thing, because eventually those live attenuated vaccines would gain strength and cause disease. But probably the fundamental reason, at least what I hypothesized, that they would be able to elicit protection was because of that persistence.”
So, they looked for another persistent virus that was not pathogenic, which might generate T cell immune response.
“The virus that we selected was a virus called cytomegalovirus (CMV), which is actually a virus from a different family of viruses altogether, but it’s one that most people in the world are infected with. But it’s unique in that you can re-infect these people with a virus that now has within its genes HIV genes and then the body would make immune responses to those HIV genes,” he said.
The HIV genes that would be placed in the harmless virus, he said, would not cause disease.
“When they’re introduced into the vaccinee, the immune response recognizes these HIV bits as if they’re part of CMV and raises immune response to it,” he said.
That’s the plan, anyway. The difficult part is making a version of the vaccine that’s safe and effective for humans. That requires an approved vaccine candidate and years of clinical trials.
Meanwhile, in Thailand, a follow-up study is getting underway of the RV 144 vaccine candidate. Several years ago, a study showed that it did indeed provide some measure of protection against HIV, but not enough, being only 31 percent effective. A clinical study called RV 305 will use the same vaccine components as RV 144, but will attempt to boost and extend the immune response through antibodies.