Research Profile – A Sweet Source to an HIV Vaccine?
The sugar clusters on a harmless bacterium could be the key to developing an HIV vaccine.
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Dr. Ralph Pantophlet
A British Columbia researcher may have found a detour around the roadblock to a human immunodeficiency virus (HIV) vaccine.
Dr. Ralph Pantophlet of Simon Fraser University has discovered that a strain of the harmless plant bacterium Rhizobium radiobacter has surface sugar molecules that closely resemble those found on HIV-1, the most common strain of the virus.
A sugar twin?
"Not quite a twin," says Dr. Pantophlet, a 2009 CIHR New Investigator and recipient of a prestigious Scholar Award from the Michael Smith Foundation for Health Research. "Maybe a sister or a brother. As close as one could probably find in nature."
One of the major goals in HIV research is the design of a vaccine component to trigger the immune system to produce antibodies to protect against a wide range of HIV strains. However, researchers around the world have faced challenges. While hopes were high that the Thailand-based RV144 study would produce strong outcomes, the rate of HIV infection was only 31% lower among participants who received the experimental vaccine compared to those who received a placebo.
A devious virus, HIV tends to stay a step ahead of the immune system. The antibody response to its surface protein, the so-called HIV "spike," usually does not occur until several weeks after infection. The immune system simply does not register its presence.
Until recently, researchers believed HIV's sugar molecules provided something akin to a cloak of invisibility, allowing HIV to enter and move about without detection until after infection takes hold. But that thinking is now under revision.
"Newer technology has allowed researchers to go in and recover huge numbers of antibodies from HIV-infected individuals, some of whom show you can get good antibodies to these sugar molecules," says Dr. Pantophlet. "The objective now is to figure out how to do this with a vaccine formulation."
Dr. Pantophlet and his colleagues hypothesize that the Rhizobium sugar molecules can be formulated so that, when injected into the body, the immune system produces antibodies. Because the sugar molecules look so much like their HIV counterparts, the immune system's "memory" would then spring into action when the real HIV invader makes an appearance – repelling the virus before it takes hold.
Early tests, the results of which were published this year in Chemistry & Biology, show promise, says Dr. Pantophlet.
"We made a bacterial suspension and put it into small animals, asking the question, 'Will the animals respond to this bacterial molecule?' We took blood from the animals to see if it contained antibodies that recognized the bacterial sugar and observed that not only was that the case but we also could get some cross-reaction to the HIV molecule, suggesting that we are headed in the right direction."
Two pharmaceutical companies have expressed interest in supplying Dr. Pantophlet's team with "carrier proteins," commonly used for making sugar-based vaccines, to further expand on the animal work and determine if it might be extended to people.
Dr. Dennis Burton of the Scripps Research Institute in California is a leading researcher in development of broadly neutralizing antibodies to fight variable pathogens like the AIDS virus. He sees Dr. Pantophlet's Rhizobium findings as helping to find the way forward in the quest for a vaccine.
"It's beautiful research and very valuable information for the field. The significance of Ralph's work is that it's a potential signpost on the way to a vaccine. It's quite provocative in suggesting novel strategies for vaccine design."
"My undergraduate and graduate training is in medical and biochemical microbiology. I was wondering 'What if there was a bacterium that made much the same kind of sugar molecule as on HIV?'."
– Dr. Ralph Pantophlet, Simon Fraser University
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