Vaccine makes headway against trachoma
Experimental immunization may boost fight against blinding disease
By deleting a key component in a bacterium that causes a blinding infection called trachoma, scientists have developed a vaccine that might protect against the disease. Monkeys given the experimental vaccine become partially or totally immune to Chlamydia trachomatis, the microbe that causes the condition, researchers report online October 10 in the Journal of Experimental Medicine.
“I think this is promising, to finally see some results in vaccine development,” says physician Danny Haddad, director of the International Trachoma Initiative, a nongovernmental organization based in Decatur, Ga., who was not involved in the study. Haddad cautions that it could still take many years before a vaccine reaches the public, but allows that “it could be a very helpful tool within the global strategy against trachoma.” That approach now centers on improving hygiene, dosing whole villages with antibiotics, and providing eye surgery as needed (SN: 2/23/08, p. 116).
The new findings also raise the possibility that such a vaccine might work against a better-known strain of C. trachomatis — the one that causes the sexually transmitted disease chlamydia. “It’s suggestive of that, but suggestions are always risky,” says study coauthor Harlan Caldwell, a microbiologist at the National Institutes of Health’s Rocky Mountain Laboratories in Hamilton, Mont. Still, he adds, “I think [the vaccine] would be highly likely to have a reasonable effect against other chlamydial diseases.”
C. trachomatis is spread by interpersonal contact and by flies. In the study, six cynomolgus macaques received three doses each of the vaccine in eyedrops over the course of a few months, while six others weren’t vaccinated. One month after the last vaccine dose, all 12 monkeys were given eyedrops containing a highly virulent strain of C. trachomatis and were then monitored weekly.
The unvaccinated monkeys showed moderate to severe eye disease for two to four months. In contrast, three of the vaccinated monkeys demonstrated strong immunity to the bacterium, remaining free of eye disease. The other three had partial immunity, characterized by significantly less infection immediately after exposure compared with the unvaccinated controls — which also made them less likely to spread the microbe. Just one vaccinated monkey still showed signs of infection six weeks later. After 14 weeks of observation, monkeys with any lingering infection were treated with antibiotics to cure them.
To make the vaccine, the scientists deleted a key component of C. trachomatis, a ring of DNA called a plasmid that was suspected to play a role in the disease. The eye damage caused by trachoma results less from the microbe itself than from the immune system’s response to it. The infection triggers a “hyper-reaction” of inflammation of the eyelid, Caldwell says, which swells and eventually can turn inward. Over time, the eye lashes scratch the cornea, leading to scarring and blindness.
The plasmid encodes a protein whose function is unknown, so exactly how the vaccine works is unclear. Caldwell suspects the plasmid “is driving a very strong innate immune response that, in a sense, becomes the pathology” for the infection. Removing the plasmid might allow a more specific immune reaction against the microbe with fewer harmful effects, he says.
The researchers are working on that puzzle. The team is also testing the vaccine in more monkeys and is seeking regulatory approval to test it in people, Caldwell says.
