Scientists at Johns Hopkins and the University of Massachusetts have developed an unusual vaccine that may prevent or speed recovery from chlamydia, the world's leading cause of infectious blindness and sexually transmitted diseases. The vaccine is the first to use successfully only a purified anti-chlamydial antibody in a vaccine to immunize against and stop this infectious disease.
In animal experiments supported by the National Institutes of Health, the Edna McConnell Clark Foundation and Research to Prevent Blindness, the vaccine protected mice from eye infections with Chlamydia trachomatis.
"This is an important step toward making a vaccine for humans," says Judith A. Whittum-Hudson, Ph.D., associate professor of ophthalmology and a research at Wilmer Eye Institute at Hopkins. "But it will require further development and tests in other animal models before it will be available to people." Whittum-Hudson is senior author on the report of this study, published in the October issue of Nature Medicine.
Antibodies are proteins produced by certain cells of the immune system that recognize and help destroy foreign substances in the body. Until now, most successful vaccines have been made either from the entire infectious organism that causes a disease, or a purified part of that organism. Such vaccines trigger production of antibodies that latch onto the organism and either kill it, inactivate it, or signal other parts of the immune system to join the battle against the infection.
The new vaccine, called anti-idiotype, is an antibody with the same shape as a piece of the germ, a bacterium, that naturally provokes the immune system into action, according to Whittum-Hudson. The vaccine is not an antibody against the organism. Rather, the antibody against the organism is used to stimulate production of a second antibody. This second antibody is the vaccine.
"The development of this vaccine is important because people can get the disease more than once. They don't build up resistance to it as they do to many other infections," she says. That may be because the immune response to this organism is too weak to prevent another infection. Thus, the bacteria repeatedly infect mucus membranes, like the inside of the eyelid or the genital tract, causing inflammation and damage.
The Hopkins-Massachusetts team used a trick of immunology to produce protein in the shape of GLXA, a substance produced by all chlamydial bacteria. Because GLXA is made of carbohydrate and fat instead of protein, it does not stimulate an effective response from the immune system, according to Whittum-Hudson. "But the anti-idiotype antibody vaccine is a protein, which stimulates the immune system more effectively than the real GLXA alone, or even the entire organism," she says.
When injected or fed to mice, the anti-idiotype stimulated the mouse to produce effective and long-lasting protection against C. trachomatis. The vaccine was effective even when given by mouth because it was put into a biodegradable capsule resembling plastic. The coating protected the antibody from the stomach's acid digestive juice so it could reach those sites in the intestinal tract that are part of the immune system.
C. trachomatis affects 700 million people worldwide.
Other authors of the article include Ling-Ling An and A. Bruce MacDonald (University of Massachusetts, Amherst) and W. Mark Saltzman and Robert A. Prendergast (Johns Hopkins).