Antibody Warfare: Vaccine halts microbes in dialysis patients

By inducing the immune system to do a job that antibiotics sometimes can’t, scientists have found a way to fend off a microbe that causes deadly blood infections.

The researchers fashioned a vaccine against the troublesome bacterium Staphylococcus aureus by packaging two of the microbe’s own carbohydrate molecules with a protein that the immune system recognizes as foreign. This generates enough antibodies to defend against S. aureus in many kidney-dialysis patients, who are susceptible to staph infections, researchers report in the Feb. 14 New England Journal of Medicine.

Roughly one-fourth of all people at any given moment have S. aureus in or on their bodies. In most cases, the immune system or antibiotics kill off the bacteria. But by a Darwinian selection process, S. aureus strains that survive in hospitals and nursing homes–where many people are on long-term antibiotics–often become resistant to drugs.

In the first large trial of a vaccine against S. aureus in people, the researchers vaccinated roughly half of 1,798 dialysis patients. Such people are vulnerable to staph infections because their kidneys don’t clear waste products from the blood efficiently and because they have shunts. These devices–installed through the skin to allow blood to flow in and out during dialysis–increase the risk of infection, says study coauthor Ali I. Fattom of Nabi, a pharmaceutical company in Rockville, Md.

In the trial, he and his colleagues found that only 11 of 892 dialysis patients had S. aureus in their blood during the 40 weeks following a single injection of the vaccine, whereas 26 of 906 unvaccinated dialysis patients had a staph infection.

The staph infections that arose in vaccinated patients also developed later than in the other group, notes Naomi Balaban of the University of California, Davis. This is encouraging because it suggests that vaccination will keep dialysis patients free of infection longer, she says.

The study “represents a major advance in our prevention of staphylococcal disease,” says Larry M. Baddour of the University of Tennessee Medical Center in Knoxville. This and other antibacterial vaccines are ushering in a decade of progress against these microbes, he says.

The human immune system tends to overlook carbohydrate molecules, so Fattom and his colleagues built the vaccine by attaching the two microbial carbohydrates to an engineered version of a protein from another bacterium.

The combination elicited an immune response.

Since the carbohydrate molecules are integral parts of a capsule structure that normally shields S. aureus, it’s unlikely the bacterium will change in response to the vaccine and become resistant, Fattom says.

The new vaccine arrives at a time when antibiotic designers are struggling “to stay one step ahead of [drug-]resistant bacteria,” says Fattom.

Despite sterilizing techniques, invasive procedures now available–such as catheters threaded through blood vessels to the heart–expose many patients to S. aureus infection, says J. John Weems of the Greenville

Hospital Systems in Greenville, S.C. The vaccine may prove useful for any patient entering a hospital for elective surgery, says study coauthor John B. Robbins of the National Institute of Child Health and Human Development in Bethesda, Md.

Only a thorough cost-benefit study will determine whether doctors should give the vaccine to all patients undergoing such procedures, Weems says.

Because the vaccine didn’t protect all the people who got it, the researchers are now attempting to make it more potent by adding a third carbohydrate molecule from the S. aureus capsule, Fattom says.