AIDS vaccine candidate appears to completely clear virus from the body in monkeys

Sep. 11, 2013 — An HIV/AIDS vaccine candidate developed by researchers at Oregon Health & Science University appears to have the ability to completely clear an AIDS-causing virus from the body. The promising vaccine candidate is being developed at OHSU's Vaccine and Gene Therapy Institute. It is being tested through the use of a non-human primate form of HIV, called simian immunodeficiency virus, or SIV, which causes AIDS in monkeys. Following further development, it is hoped an HIV-form of the vaccine candidate can soon be tested in humans.

These research results were published online today by the journal Nature. The results will also appear in a future print version of the publication.

"To date, HIV infection has only been cured in a very small number of highly-publicized but unusual clinical cases in which HIV-infected individuals were treated with anti-viral medicines very early after the onset of infection or received a stem cell transplant to combat cancer," said Louis Picker, M.D., associate director of the OHSU Vaccine and Gene Therapy Institute. "This latest research suggests that certain immune responses elicited by a new vaccine may also have the ability to completely remove HIV from the body."

The Picker lab's approach involves the use of cytomegalovirus, or CMV, a common virus already carried by a large percentage of the population. In short, the researchers discovered that pairing CMV with SIV had a unique effect. They found that a modified version of CMV engineered to express SIV proteins generates and indefinitely maintains so-called "effector memory" T-cells that are capable of searching out and destroying SIV-infected cells.

T-cells are a key component of the body's immune system, which fights off disease, but T-cells elicited by conventional vaccines of SIV itself are not able to eliminate the virus. The SIV-specific T-cells elicited by the modified CMV were different. About 50 percent of monkeys given highly pathogenic SIV after being vaccinated with this vaccine became infected with SIV but over time eliminated all trace of SIV from the body. In effect, the hunters of the body were provided with a much better targeting system and better weapons to help them find and destroy an elusive enemy.

"Through this method we were able to teach the monkey's body to better 'prepare its defenses' to combat the disease," explained Picker. "Our vaccine mobilized a T-cell response that was able to overtake the SIV invaders in 50 percent of the cases treated. Moreover, in those cases with a positive response, our testing suggests SIV was banished from the host. We are hopeful that pairing our modified CMV vector with HIV will lead to a similar result in humans."

The Picker lab is now investigating the possible reasons why only a subset of the animals treated had a positive response in hopes that the effectiveness of the vaccine candidate can be further boosted.

This research was funded by several grants from the National Institutes of Health, funding from the International AIDS Vaccine Initiative and a CAVD grant from the Bill & Melinda Gates Foundation.

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HIV-like virus 'cleared in monkeys'

11 September 2013 Last updated at 17:26 GMT By Rebecca Morelle Science reporter, BBC World Service The team looked at a form of SIV that is up to 100 times more deadly than HIV A vaccine for the monkey equivalent of HIV appears to eradicate the virus, a study suggests.

Research published in the journal Nature has shown that vaccinated monkeys can clear Simian Immunodeficiency Virus (SIV) infection from their bodies.

It was effective in nine of the 16 monkeys that were inoculated.

The US scientists say they now want to use a similar approach to test a vaccine for HIV in humans.

Prof Louis Picker, from the Vaccine and Gene Therapy Institute at Oregon Health and Science University, said: "It's always tough to claim eradication - there could always be a cell which we didn't analyse that has the virus in it. But for the most part, with very stringent criteria... there was no virus left in the body of these monkeys."

Search and destroy

The research team looked at an aggressive form of virus called SIVmac239, which is up to 100 times more deadly than HIV.

Infected monkeys usually die within two years, but in some inoculated primates the virus did not take hold.

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It maintains an armed force, that patrols all the tissues of the body, all the time, indefinitely”

End Quote Prof Louis Picker Oregon Health and Science University The vaccine is based on another virus called cytomegalovirus (CMV), which belongs to the herpes family.

It used the infectious power of CMV to sweep throughout the body. But instead of causing disease, it has been modified to spur the immune system into action to fight off the SIV molecules.

"It maintains an armed force, that patrols all the tissues of the body, all the time, indefinitely," explained Prof Picker.

The researchers gave rhesus macaque monkeys the vaccine, and then exposed them to SIV.

They found that at first the infection began to establish and spread. But then the monkeys' bodies started to respond, searching out and destroying all signs of the virus.

Of the monkeys that successfully responded to the vaccine, they were still clear of infection between one-and-a-half and three years later.

Prof Picker said his team was still trying to work out why the vaccination worked in only about half of the monkeys.

"It could be the fact that SIV is so pathogenic that this is the best you are ever going to get.

"There is a battle going on, and half the time the vaccine wins and half the time it doesn't," he said.

Human trials

The researchers are now testing the vaccine to see if it can be used after SIV exposure to treat and potentially cure infected monkeys.

They also want to see if the technique could work in humans.

Prof Picker said: "In order to make a human version we have to make sure it is absolutely safe.

The researchers now want to move from monkeys to test the vaccine in humans

"We have now engineered a CMV virus which generates the same immune response but has been attenuated [modified to lose its virulence] to the point where we think it is unequivocally safe."

This would first have to pass through the regulatory authorities, but if it does, he said he hoped to start the first clinical trials in humans in the next two years.

Commenting on the research, Dr Andrew Freedman, from Cardiff University School of Medicine, said: "This suggests that prophylactic vaccines - vaccines designed to prevent infection - using CMV vectors may be a promising approach for HIV.

"While they may not prevent the initial infection, they might lead to subsequent clearance, rather than the establishment of chronic infection."

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