A novel method for strengthening current vaccines could improve immune response to certain groups of bacteria. The method, described in the January issue of Nature Medicine, could be of great value in providing better protection to infants and AIDS patients against life-threatening diseases such as pneumonia and meningitis. It may also provide an inexpensive way of preventing epidemics in developing countries, the study's authors say.
When the immune system's T cells detect a bacterial protein, they become activated and ready to fight the intruder. They also rally forces by docking to the CD40 receptor of B cells, stimulating these cells to manufacture potent immunoglobulin G (IgG) antibodies that can inactivate foreign proteins. But some bacteria evade detection by coating themselves in a thick sugar capsule made of polysaccharides, which hides their telltale bacterial proteins. When infected by these kinds of bugs, adults must rely on less effective IgM antibodies, and children less than 2 years old are defenseless.
Current vaccines activate T cells and thus the CD40 receptor by using purified bacterial proteins attached to a number of different polysaccharides. But because the bacteria can have any of more than 80 different polysaccharides, it is difficult to include them all in the vaccines. So the vaccines don't provide immunity against all strains.
Andy Heath of the University of Sheffield Medical School in the United Kingdom and colleagues have bypassed these problems by creating a vaccine that activates the B cells directly, without relying on T cells. Heath's team tacked an antibody designed to bind with CD40 onto their polysaccharide vaccine preparation against Streptococcus pneumoniae. When mice were immunized with the vaccine, they produced a 50-fold higher concentration of the potent IgG-type antibodies as compared to mice injected with the standard polysaccharide vaccine.
"I think it's a very clever idea," says Jean Lee, a microbiologist at the Brigham and Women's Hospital at Harvard Medical School in Boston, Massachusetts. But she points out a limitation: The increased immune response also leads to production of autoantibodies--antibodies against normal proteins in the body. Heath believes that this side effect should disappear as the dosage of the CD40 antibody is reduced to the minimum amounts required. And he adds that the new technique is simpler and much less expensive than having to purify proteins and attach them to the polysaccharides.