Scientists have taken an important step toward creating a vaccine against Alzheimer’s disease, customizing the response of the immune system with unprecedented precision.
Using a harmless form of the herpes virus, scientists at the University of Rochester Medical Center put into mice a payload of genetic information that created a carefully crafted immune response, one that muted the type of toxic side effects seen in a previous study in people of a vaccine against Alzheimer’s. The work was published on-line June 25 in Neurobiology of Aging.
Though the current study was not in people but in mice, researchers are excited because it demonstrates a level of control over an Alzheimer’s vaccine that was previously unattainable.
“This work provides a platform to shuffle the immune response, a flexibility to modify the approach to create a vaccine that is safe and efficacious,” says Howard Federoff, M.D., Ph.D., professor of neurology and director of the Center for Aging and Developmental Biology. “This points the way toward shaping and modulating the exact immune response needed to fight or prevent Alzheimer’s disease.”
In a previous study, other researchers showed that a potential vaccine designed to protect against Alzheimer’s was apparently effective in some people – but the vaccine caused severe inflammation in the brains of several participants, and the study was halted last year because of the danger.
With funding from the National Institutes of Health, Federoff and William Bowers, Ph.D., assistant professor of Neurology, set out to create a vaccine without the harmful side effects, by boosting part of the immune system not responsible for the side effects. And they succeeded: While a vaccine most like the previous form proved lethal to four out of six mice, a modified form of the vaccine, additionally equipped with a tetanus toxin to alter the immune response, proved much safer while still causing a 20-percent decline in the amount of amyloid plaque in the brain. The additional antigen tweaked the immune response in a way that muted the original vaccine’s harmful side effects.
“From our studies and those of others, it appears that you need to induce specific immune activity to clear existing plaque or prevent the formation of new plaque deposits,” says Bowers. “In essence, we want the beneficial effects of the vaccine without the toxicity. The herpes vector system gives us the flexibility to fine-tune the nature of the immune response so we can possibly create an effective vaccine that has a more optimal safety profile.”