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2005 Grant - Chackerian

Vaccines Against Beta-Amyloid Using Conjugated Virus-Like Particles

Bryce Chackerian, Ph.D.
University of New Mexico
Albuquerque, New Mexico

2005 New Investigator Research Grant

One of the hallmarks of Alzheimer's disease is the accumulation in the brain of a small protein fragment called beta-amyloid. Some evidence also suggests that this fragment is toxic and that it may even be responsible for many facets of the disease, including neurodegeneration and subsequent loss of memory and mental capacity. For this reason, drugs or therapies that promote removal of beta-amyloid from the brain are being actively pursued.

One treatment strategy that has proven effective in mice with an Alzheimer-like disorder is the stimulation of the animal's own immune system to scavenge beta-amyloid. This vaccine-like therapy against the protein fragment has also been tried in humans, but it led to dangerous side effects in some volunteers. This was because the vaccine activated certain types of immune cells that cause inflammation in the brain.

Bryce Chackerian, Ph.D., and colleagues will use a different type of vaccination method to promote beta-amyloid clearance while circumventing inflammatory side effects. The idea is to coat harmless, noninfectious, virus-like particles with the amyloid protein. The virus-like particles will help trick the immune system into attacking beta-amyloid, which would otherwise be ignored because it is not a foreign protein. But unlike the vaccine that has been used in clinical trials, the virus-like particles should not activate the immune cells that cause inflammation.

The researchers have already used this method to vaccinate animals against a variety of proteins. The beta-amyloid vaccine will first be tried in mice that have an Alzheimer-like pathology. If the strategy works, it could lead to a new generation of safer vaccines for Alzheimer's disease.