New study could 'significantly contribute' to development
by Mike Andrew -
SGN Staff Writer
Research conducted at Oregon Health & Science University's Vaccine and Gene Therapy Institute (VGTI) may offer hope for an eventual HIV vaccine.
In a study published in the journal Nature on May 11, researchers reported that they had developed a vaccine that was effective in preventing SIV (Simian Immunodeficiency Virus) infections in rhesus macaques.
SIV is the monkey equivalent of HIV in humans, and tests on monkeys are the standard precursor to human testing.
The VGTI researchers said their study could 'significantly contribute' to the development of an effective HIV vaccine.
The researchers gave 24 healthy rhesus macaques a vaccine containing a genetically modified form of the virus rhesus cytomegalovirus (CMV).
In 13 of the monkeys, the vaccine appeared to offer protection against SIV. Of these 13, 12 monkeys were still protected one year into the experiment.
The researchers say the vaccine works by stimulating the production of a particular type of blood cell, called 'effector memory T-cells,' which can remain vigilant in the body long after an infection has abated.
Lead author VGTI Professor Louis J. Picker compared these cells to soldiers being held in reserve.
'There are soldiers that are back at the base with their rifles in the shed, and then you have the guys out in the field,' he said.
There was also evidence, Picker added, that the vaccine all but eradicated traces of SIV in the monkeys, something which is 'unprecedented' in HIV vaccine research.
CMV is related to herpes, generally has no symptoms, is thought to already infect most humans, and tends to stay in the system forever.
Researchers hoped that such a persistent virus might be able to keep human antibodies constantly active against another long-living virus like HIV.
Professor Sir Andrew McMichael of Oxford University told BBC News that HIV arose from a type of SIV found in chimpanzees, so the animal model used in the VGTI study was promising.
'I'm excited by the science because it really does demonstrate that it may be possible to eradicate the HIV virus by a strong immune response,' he said.
'But at the same time I'm scratching my head how to take this approach into humans.'
The problem, McMichael said, was potential safety and regulatory issues with introducing CMV into humans, even though many of us already carry the virus.
'CMV is not totally benign, it does cause a number of diseases. If you're giving people something you're not going to be able to get rid of should it cause problems, then that's quite a difficult risk to manage.'
Professor Robin Shattock of Imperial College, London, agreed safety would be key.
'The breakthrough here is in using a viral-delivered vaccine that persists - essentially using an engineered virus to thwart a pathogenic virus,' he told BBC. 'The tricky part will be showing it is safe and effective in humans.'
VGTI's Picker responded by saying such issues would be addressed in forthcoming work, pointing out that early forms of the smallpox vaccine also carried health risks to humans.
'On one level 99% of people in sub-Saharan Africa are CMV-positive and half the people in the developed world are, so we know a lot about it and it's mostly non-pathogenic, except in vulnerable populations like pregnant women,' he said.
'We're fully aware that to make it available to humans, the next step is to make a virus which retains or has an enhanced ability to make effector memory cells, but no longer has the capacity to infect vulnerable parts of the population.'
In the wake of the Nature article, VGTI revealed on May 13 that they hoped to test their vaccine on human subjects at facilities in Florida.
Dr. Jay Nelson, executive director and vice president of VGTI Florida, said the vaccine could be ready for clinical trials on humans in three years.
'The experiments we've done raise a lot of hope for a vaccine that'll provide protection for the majority of people,' Nelson said.
'We're taking one persistent infection [HIV] and fighting it with another [CMV], and it works.'
Nelson added that VGTI Florida is currently working on how to make the vaccine safer for humans, particularly for those groups with pre-existing health conditions.
Future research could include collaboration with Martin Memorial Health Systems, Nelson said. Martin Memorial's new 80-bed hospital is slated to open next door to VGTI Florida's facilities in 2014.
According to spokesperson Scott Samples, Martin Memorial has already been in talks with VGTI about various HIV trials.
VGTI Oregon has been researching the vaccine for more than 10 years with federal grant money from the National Institutes of Health, and additional funding from the International AIDS Vaccine Initiative (IAVI).
The project received $1.06 million from NIH in 2010 and received similar amounts in 2008 and 2009, according to the NIH website.
For the previous five years, NIH funded the project at about $700,000 per year.
'When the time comes, if they're [VGTI] looking for assistance from Martin Memorial, we'll see if we can accommodate that, and we look forward to having the opportunity to help them further their research,' Martin Memorial's Samples said.
NIH is an agency of the U.S. Department of Health and Human Services.
IAVI is an independent agency that helps fund research and clinical assessment of HIV vaccines with a special focus on 'the developing world, where some 95% of new HIV infections occur.'
According to its website, IAVI and its partners have developed 17 possible vaccines, nine of which have entered human trials in 11 countries.
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