A shot consisting of a single bacterial protein can prevent pneumonia in mice, a study in the April Nature Medicine suggests. If effective in humans, the vaccine could help control a dangerous form of pneumonia that mainly afflicts hospitalized patients and individuals with cystic fibrosis. And the approach may have a broader application as well. If the analogous proteins can be identified in other common bacterial pathogens, such as Salmonella or Chlamydia, experts say, they might prove useful for warding off those infections.
The pneumonia in question is caused by Pseudomonas aeruginosa, a common soil bacterium, which each year kills tens of thousands of individuals in the United States alone. Most of the victims acquire the infection while in the hospital or have predisposing conditions such as a weakened immune system. Pseudomonas attacks and eventually kills cells by injecting them with toxins. In earlier work, the team of microbiologist Dara Frank at the Medical College of Wisconsin in Milwaukee had identified genes that give Pseudomonas its deadly sting. They turned out to work similarly to genes in an unrelated bug, Yersinia pestis, the cause of bubonic plague. Because animals vaccinated with the protein produced by one of those Yersinia genes are immune to the plague, Frank wondered whether shots with the respective Pseudomonas protein, called PcrV, could offer the same protection against pneumonia.
The team immunized mice with either PcrV or antibodies to it. When they subsequently infected the animals with Pseudomonas, both vaccinated groups suffered almost no lung damage. Animals not vaccinated all died. In a separate set of experiments, Frank showed that the PcrV antibodies prevented the bacterium from shooting its toxin into cells, including macrophages, the immune system's scavenger cells, which are particularly vulnerable to Pseudomonas. "When macrophages attack Pseudomonas to get rid of it, the bacterium turns around and shoots them," Frank says. "But the antibodies neutralize the bacteria, so the macrophages can now eat the bugs and kill them."
The findings give Robert Brubaker, a microbiologist at Michigan State University in East Lansing, "every reason to be optimistic." Given the frequency and severity of Pseudomonas infections, he says, "a vaccination against it could be a spectacular public health achievement." For now, the biggest target group for a Pseudomonas vaccine would be cystic fibrosis patients. But eventually, Brubaker says, proteins related to PcrV and its Yersinia cousin could help prevent infections caused by bacteria other than Pseudomonas.