Evidence is mounting that several devastating illnesses, including multiple sclerosis and late-onset Alzheimer’s disease, may have ties to an infection with a ubiquitous bacterium known as Chlamydia pneumoniae. Usually, the human body’s natural defenses are effective in fighting off this respiratory pathogen, but in patients with a genetic predisposition to certain diseases, the infection appears to trigger onset of the illnesses.

A WSU professor is part of a multidisciplinary and multi-institutional team that is developing a vaccine against the closely related C. trachomatis bacterium. Preliminary data indicate the vaccine should also fight other members of the Chlamydia species, including C. pneumoniae, said Judith Whittum-Hudson, PhD, WSU professor of internal medicine (rheumatology), immunology and microbiology, and ophthalmology.

Dr. Whittum-Hudson’s involvement in the vaccine development grew from a long-term interest in the sexually transmitted C. trachomatis, which is the leading cause worldwide of STDs. In developing countries, it is the leading cause of preventable infectious blindness (trachoma). “I had been working with the late Bruce MacDonald and his immunochemistry group at the University of Massachusetts (Amherst). He was trying to isolate various Chlamydia antigens mostly for diagnostic purposes,” she said. He and Dr. Elizabeth Stuart, who continues the U-Mass. Studies, identified a glycolipid antigen that the bacterium produced and began to consider it as a possible vaccine target.

“The problem was that it was not a glycoprotein,” she said, explaining that proteins elicit an immune response through T-cells that essentially remember previous infections and these memory cells can quickly respond to subsequent assaults. “The immune response to a glycolipid, however, would not involve T-cell memory. That means that if somebody were vaccinated with the glycolipid, they would have to be revaccinated, revaccinated and revaccinated.”

Their solution was to create a protein vaccine to mimic the lipid’s structure. The specially designed protein, a socalled anti-idiotypic antibody, would then induce the T-cell responses to the glycolipid and allow the immune system to recognize and respond to future bacterial infections without continual vaccinations. “The immune system of the animal or person theoretically would think that it’s being immunized with that glycolipid, but it really isn’t. This is really exciting work,” she explained. Preclinical studies of the vaccine against C. trachomatis are almost completed.

While the vaccine investigations continued, Dr. Whittum-Hudson became involved in a project on Alzheimer’s disease through a collaboration with Brian Balin, Todd Abrams and her husband Alan Hudson. Hudson, PhD, is a professor of immunology and microbiology at Wayne State. “We showed that in a reasonable- sized population of late-onset Alzheimer’s patients, C. pneumoniae was present at the site of the neuropathology in the brain.”

That finding, in conjunction with other more recent research reports demonstrating links between the bacterium and both atherosclerosis and multiple sclerosis, prompted Drs. Whittum-Hudson and Hudson to begin another project with Robert Swanborg, PhD, WSU professor of immunology and microbiology. Dr. Swanborg has an international reputation for his work with a rodent model of human multiple sclerosis. In the rodent model and in MS, the body’s immune system attacks and destroys the myelin sheath, which is the insulation surrounding nerves in the brain. Swanborg’s lab, and particularly doctoral student Derek Lenz, identified a peptide on C. pneumoniae that looked similar enough to part of the primary protein on the myelin sheath to basically fool the immune system and initiate the damaging attack on the myelin sheath.

These results strengthen the hypothesis that the bacterium may well play an important role in disease onset, at least in a subset of MS patients. It also gives Dr. Whittum-Hudson added ammunition in her quest to have the C. trachomatis vaccine tested for its efficacy against C. pneumoniae and other chlamydial species known to cause disease.

“This vaccine is one that theoretically could work against C. pneumoniae as well as C. trachomatis. The glycolipid antigen and mimic are genus-specific, so I have a vision of vaccinating babies, boosting them when they’re teenagers to protect against sexually transmitted diseases, boosting them when they’re 50 to protect them against atherosclerosis and cardiovascular disease, and boosting them again when they’re 70 to protect them against Alzheimer’s disease.” Along the way, she also envisions the vaccine conferring protection against multiple sclerosis and other chronic diseases in which chlamydial species are implicated.