Getting closer to HIV cure

Getting closer to HIV cure
Acquired immunodeficiency syndrome or AIDS continues to be a major disease, killing over three million people every year globally. Some 42 million continue to suffer the effects of AIDS or the HIV virus. New HIV virus touch 5 million people every year. Despite extensive research, a cure for human immunodeficiency virus has still alluded us, with a combination drug therapy providing some relief.

But recently, researchers from Thomas Jefferson University in the US may have brought us one step closer to developing a vaccine against AIDS. Led by Matthias J Schnell, director of the Jefferson Vaccine Center, the researchers found that a rabies virus-based vaccine administered to monkeys protected them against the simian equivalent of the HIV virus or SIV. The data has been published in Vaccine.

The researchers previously showed that a rabies-based vaccine possessing HIV and SIV antigens protected against a chimeric HIV/SIV in monkeys. In this study, they used an attenuated rabies virus to protect against a highly pathogenic variety of the simian virus called SIVmac251. This type of SIV causes a disease in monkeys similar to one in humans infected with HIV-1. In addition, it is difficult to protect monkeys against AIDS-like disease after challenge with the SIVmac251.

Two vaccine strategies were used: immunisation with a recombinant rabies virus or a combination of that and a rabies virus. Both strategies induced neutralising antibody production and increased protection against SIV. Although the combination with rabies virus helped immediately following the infection, the long-term benefits were minimal. However, it was surprising that the rabies-based vaccine was able to induce such potent anti-SIV responses.

“Although we can't yet block the infection, we showed that we can protect against disease,” said Dr Schnell. “We also saw significant antibody activity against the virus, which is promising. In addition, this is a very simple approach that only took two immunisations.”

Earlier in April 2007, in the Journal of Infectious Diseases, the same scientists showed that two years after the initial vaccination, four vaccinated non-human primates were protected from disease, even after being “challenged” with a dangerous animal-human virus. Two control animals developed an AIDS-like disease.

Schnell and his co-workers in the earlier research tested the effects of inserting two different viral proteins into the rabies virus genome, and using such viruses-based vaccines in preventing disease in rhesus macaques. One was a glycoprotein on the surface of HIV, while the other was an internal protein from SIV. They used the latter because HIV does not cause disease in monkeys.

The idea was that such rabies’ vehicles, or “vectors,” would help attract a strong response from the animal's immune system, though the rabies virus used cannot cause the rabies disease. Such vectors are based on a type of rabies vaccine strain that has been used for more than 20 years in oral vaccines against rabies in wildlife in Europe. Again in the earlier research, the study was aimed at studying the safety and effectiveness of the rabies vaccine approach against HIV and related diseases.

Four macaques were immunized with both vaccines, while two animals received only a weakened rabies virus. After they gave the animals an initial vaccination, they then tried two different immune system boosts, but didn't see enhanced immune responses. They then developed a new vector, a viral surface protein from another virus, vesicular stomatitis virus (VSV). Two years after the initial immunisation, they gave a booster vaccine with the rabies-VSV vector, and saw SIV/HIV-specific immune responses.

The group then challenged the animals with SIV and measured various parameters of infection, such as immune system CD4 cell count, amount of virus in the bloodstream and immune system antibody response. They found that those animals that were given the test vaccine could control the infection. The control animals without the experimental vaccine had high levels of virus and a loss of CD4 cells.

“We still need a vaccine that protects from HIV infection, but protecting against developing disease can be a very important step,” Schnell says, noting that he and his colleagues aren't sure how long the viral immunity will last.

According to him, the study demonstrated a “proof of principle” — that is, that the method used is technically possible. He says that the results indicate the need for future studies in larger groups of animals, and that these currently are underway. In addition, one key question remains unanswered: Is such a rabies-based vaccine feasible as an HIV vaccine in humans? More research will tell. But Schenell and his colleagues have taken the world closer to a possible vaccine.

The writer is a doctoral scholar, Carnegie Mellon University, Pittsburgh and knowledge editor at Financial Chronicle

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